Economic evaluation of the levonorgestrel-releasing intrauterine system for the treatment of dysfunctional uterine bleeding in Spain

To compare the cost and effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) versus combined oral contraception (COC) and progestogens (PROG) in first-line treatment of dysfunctional uterine bleeding (DUB) in Spain. STUDY DESIGN: A cost-effectiveness and cost-utility analysis of LNG-IUS, COC and PROG was carried out using a Markov model based on clinical data from the literature and expert opinion. The population studied were women with a previous diagnosis of idiopathic heavy menstrual bleeding. The analysis was performed from the National Health System perspective, discounting both costs and future effects at 3%. In addition, a sensitivity analysis (univariate and probabilistic) was conducted. RESULTS: The results show that the greater efficacy of LNG-IUS translates into a gain of 1.92 and 3.89 symptom-free months (SFM) after six months of treatment versus COC and PROG, respectively (which represents an increase of 33% and 60% of symptom-free time). Regarding costs, LNG-IUS produces savings of 174.2-309.95 and 230.54-577.61 versus COC and PROG, respectively, after 6 months-5 years. Apart from cost savings and gains in SFM, quality-adjusted life months (QALM) are also favourable to LNG-IUS in all scenarios, with a range of gains between 1 and 2 QALM compared to COC and PROG. CONCLUSIONS: The results indicate that first-line use of the LNG-IUS is the dominant therapeutic option (less costly and more effective) in comparison with first-line use of COC or PROG for the treatment of DUB in Spain. LNG-IUS as first line is also the option that provides greatest health-related quality of life to patients.

Effect of maternal clinical chorioamnionitis on neonatal morbidity in very-low birthweight infants: a case control study

Aims: To assess the relationship between maternal clinical chorioamnionitis and neonatal outcome in preterm very-low birthweight (VLBW) infants. Methods: An observational case-control study was conducted in the Neonatology Services of 12 acute-care teaching hospitals in Spain. Between January 2004 and December 2006, all consecutive VLBW (F1500 g) infants born to a mother with clinical chorioamnionitis were enrolled. Controls were infants without chorioamnionitis matched by gestational age who were born immediately after each index case. Results: There were 165 cases and 163 controls. A significantly higher percentage of cases than controls required intubation (53% vs. 35.8%), had normal intrauterine growth (98.1% vs. 84.7%), were born in a tertiary center (inborn) (95.1% vs. 89.1%), from single gestations (76.4% vs. 65.6%) and vaginal delivery (47.3% vs. 33.3%), showed a lowerApgar score at 5 min, and presented a higher rate of earlyonset sepsis (10.4% vs. 1.2%). Older maternal age (32.5 vs. 30.8 years), premature labor (67.3% vs. 25.8%), premature rupture of membranes (61.3% vs. 25.8%), and antibiotic treatment (88.5% vs. 52.3%) were significantly more frequent among cases than controls. Conclusions: After controlling by gestational age, maternal chorioamnionitis was associated with neonatal depression and early sepsis but not with other prematurity-related complications.

Effect of maternal clinical chorioamnionitis on neonatal morbidity in very-low birthweight infants: a case control study

Aims: To assess the relationship between maternal clinical chorioamnionitis and neonatal outcome in preterm very-low birthweight (VLBW) infants. Methods: An observational case-control study was conducted in the Neonatology Services of 12 acute-care teaching hospitals in Spain. Between January 2004 and December 2006, all consecutive VLBW (F1500 g) infants born to a mother with clinical chorioamnionitis were enrolled. Controls were infants without chorioamnionitis matched by gestational age who were born immediately after each index case. Results: There were 165 cases and 163 controls. A significantly higher percentage of cases than controls required intubation (53% vs. 35.8%), had normal intrauterine growth (98.1% vs. 84.7%), were born in a tertiary center (inborn) (95.1% vs. 89.1%), from single gestations (76.4% vs. 65.6%) and vaginal delivery (47.3% vs. 33.3%), showed a lowerApgar score at 5 min, and presented a higher rate of earlyonset sepsis (10.4% vs. 1.2%). Older maternal age (32.5 vs. 30.8 years), premature labor (67.3% vs. 25.8%), premature rupture of membranes (61.3% vs. 25.8%), and antibiotic treatment (88.5% vs. 52.3%) were significantly more frequent among cases than controls. Conclusions: After controlling by gestational age, maternal chorioamnionitis was associated with neonatal depression and early sepsis but not with other prematurity-related complications.

Prematurity, maternal stress and mother-child interactions.

OBJECTIVE: Previous studies have shown that premature birth and the immaturity of the child can affect the quality of the parent-child relationship. The present study examines the relationship between maternal and infant interactional behavior over time and infant perinatal risk factors as well as maternal perinatal recollected traumatic experience. Few studies have explored the relationship between maternal stress and the quality of parent-infant interaction. DESIGN: Mother-child interaction was recorded at 6 and 18 months of infant's age, in a population of 47 preterm infants (GA<34 weeks) and 25 full-term infants, born in 1998, during a play interaction. According to the Care Index, sensitivity, control and unresponsiveness have been used to code maternal interactional characteristics, and cooperation, compliance-compulsiveness, difficulty and passivity have been used to code the infant's interactional characteristics. The level of maternal stress was evaluated with the Perinatal Posttraumatic Stress Disorder Questionnaire (PPQ), and the infant's perinatal risk factors were assessed with the Perinatal Risk Inventory (PERI). RESULTS: Mothers of high-risk infants, as well as mothers that had experienced traumatic stress in the perinatal period, were less sensitive and more controlling at 6 months. The interactional behavior of the preterm infant was different from that of the full-term infant at 18 months of age, and was correlated with maternal traumatic stress but not with perinatal risk factors. CONCLUSION: These results underline the importance of maternal traumatic experience related to premature birth and its potential long lasting influence on mother-child interactional behavior.

Maternal exposure to polychlorinated biphenyls and the secondary sex ratio: an occupational cohort study.

Background: Though commercial production of polychlorinated biphenyls was banned in the United States in 1977, exposure continues due to their environmental persistence. Several studies have examined the associationbetween environmental polychlorinated biphenyl exposure and modulations of the secondary sex ratio, with conflicting results.Objective: Our objective was to evaluate the association between maternal preconceptional occupational polychlorinated biphenyl exposure and the secondary sex ratio.Methods: We examined primipara singleton births of 2595 women, who worked in three capacitor plants at least one year during the period polychlorinated biphenyls were used. Cumulative estimated maternal occupationalpolychlorinated biphenyl exposure at the time of the infant's conception was calculated from plant-specific job exposure matrices. A logistic regression analysis was used to evaluate the association between maternalpolychlorinated biphenyl exposure and male sex at birth (yes/no).Results: Maternal body mass index at age 20, smoking status, and race did not vary between those occupationally exposed and those unexposed before the child's conception. Polychlorinated biphenyl-exposed mothers were, however, more likely to have used oral contraceptives and to have been older at the birth of their first child than non-occupationally exposed women. Among 1506 infants liveborn to polychlorinated biphenyl-exposedprimiparous women, 49.8% were male; compared to 49.9% among those not exposed (n = 1089). Multivariate analyses controlling for mother's age and year of birth found no significant association between the odds of amale birth and mother's cumulative estimated polychlorinated biphenyl exposure to time of conception.Conclusions: Based on these data, we find no evidence of altered sex ratio among children born to primiparous polychlorinated biphenyl-exposed female workers.

Family Alliance as a Moderator of the Link Between Maternal Postpartum Depression and Child Symptoms Assessed by Both Parents

We investigated the moderating effect of family relationships on the links between maternal postpartum depression and child symptoms in a low-risk community sample of families with 3-month-old infants (n = 57). The level of maternal depression was assessed by the Montgomery-Asberg Depression Rating Scale from a clinical interview, child symptoms by the Symptom Check List completed by both parents, and family relationships by direct observation of father-mother-baby interactions (Lausanne Trilogue Play). Families were categorized as high coordination or low coordination from their overall coordination level throughout the play. Results showed no significant links between maternal depression level and child symptoms reported by both parents. Mothers with a high depressive level in high coordination families tended to report more symptoms in their child than did mothers with lower depressive scores, whereas this link was not found in low coordination families. Prevention perspectives and clinical implications of these results are discussed.

Signalling value of maternal and paternal melanism in the barn owl : implication for the resolution of the lek paradox

Secondary sexual characters often signal qualities such as physiological processes associated with resistance to various sources of stress. When the expression of an ornament is not sex-limited, we can identify the costs and benefits of displaying a trait that is typical of its own sex or of the other sex. Indeed, the magnitude and sign of the covariation between physiology and the extent to which an ornament is expressed could differ between males and females if, for instance, the regulation of physiological processes is sensitive to sex hormones. Using data collected over 14 years in the nocturnal barn owl Tyto alba, we investigated how nestling body mass covaries with a heritable melanin-based sex-trait, females displaying on average larger black feather spots than males. Independently of nestling sex, year and time of the day large-spotted nestlings were heavier than small-spotted nestlings. In contrast, the magnitude and sign of the covariation between nestling body mass and the size of parental spots varied along the day in a way that depended on the year and parental gender. In poor years, offspring of smaller-spotted mothers were heavier throughout the resting period; in the morning, offspring sired by larger-spotted fathers were heavier than offspring of smaller-spotted fathers, while in the evening the opposite pattern was found. Thus, maternal and paternal coloration is differentially associated with behaviour or physiology, processes that are sensitive to time of the day and environmental factors. Interestingly, the covariation between offspring body mass and paternal coloration is more sensitive to these environmental factors than the covariation with maternal coloration. This indicates that the benefit of pairing with differently spotted males may depend on environmental conditions, which could help maintain genetic variation in the face of intense directional (sexual) selection.

Idiosyncratic evolution of maternal effects in response to juvenile malnutrition in Drosophila.

Maternal effects often affect fitness traits, but there is little experimental evidence pertaining to their contribution to response to selection imposed by novel environments. We studied the evolution of maternal effects in Drosophila populations selected for tolerance to chronic larval malnutrition. To this end, we performed pairwise reciprocal F1 crosses between six selected (malnutrition tolerant) populations and six unselected control populations and assessed the effect of cross direction on larval growth and developmental rate, adult weight and egg-to-adult viability expressed under the malnutrition regime. Each pair of reciprocal crosses revealed large maternal effects (possibly including cytoplasmic genetic effects) on at least one trait, but the magnitude, sign and which traits were affected varied among populations. Thus, maternal effects contributed significantly to the response to selection imposed by the malnutrition regime, but these changes were idiosyncratic, suggesting a rugged adaptive landscape. Furthermore, although the selected populations evolved both faster growth and higher viability, the maternal effects on growth rate and viability were negatively correlated across populations. Thus, genes mediating maternal effects can evolve to partially counteract the response to selection mediated by the effects of alleles on their own carriers' phenotype, and maternal effects may contribute to evolutionary trade-offs between components of offspring fitness.

Pregnancy outcome following maternal exposure to mirtazapine: a multicenter, prospective study.

This multicenter, observational prospective cohort study addresses the risk associated with exposure to mirtazapine during pregnancy. Pregnancy outcomes after exposure to mirtazapine were compared with 2 matched control groups: (1) exposure to any selective serotonin reuptake inhibitor (SSRI, control subjects with a psychiatric condition) and (2) no exposure to medication known to be teratogenic or any antidepressant (general control subjects). Data were collected by members of the European Network of Teratology Information Services between 1995 and 2011. Observations from 357 exposed pregnancies were compared with 357 pregnancies from each control group. The rate of major birth defects between the mirtazapine and the SSRI group did not differ significantly (4.5% vs 4.2%; odds ratio [OR], 1.1; 95% confidence interval [95% CI], 0.5-2.3; P = 0.9). A trend toward a higher rate of birth defects in the mirtazapine group compared with general control subjects (4.5% vs 1.9%; OR, 2.4; 95% CI, 0.9-6.3; P = 0.08) reached statistical significance after exclusion of chromosomal or genetic anomalies (4.1% vs 1.3%; OR, 3.3; 95% CI, 1.04-10.3; P = 0.03), but this difference became again nonsignificant if cases of exposure not comprising the first trimester were excluded from the analysis (3.4% vs 1.9%; OR, 1.8; 95% CI, 0.6-5.0; P = 0.26). The crude miscarriage rate did not differ significantly between the mirtazapine, the SSRI, and the general control groups (12.1% vs 12.0% vs 9.3%; P = 0.44). However, a higher rate of elective pregnancy termination was observed in the mirtazapine group compared with SSRI and general control subjects (7.8% vs 3.4% vs 5.6%; P = 0.03). This study did not observe a statistically significant difference in the rate of major birth defects after first-trimester exposure between mirtazapine, SSRI-exposed, and nonexposed pregnancies. A marginally higher rate of birth defects was, however, observed in the mirtazapine and SSRI groups compared with the low rate of birth defects in our general control subjects. Overall pregnancy outcome after mirtazapine exposure was similar to that of the SSRI-exposed control group.

Economic evaluation of the levonorgestrel-releasing intrauterine system for the treatment of dysfunctional uterine bleeding in Spain

To compare the cost and effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) versus combined oral contraception (COC) and progestogens (PROG) in first-line treatment of dysfunctional uterine bleeding (DUB) in Spain. STUDY DESIGN: A cost-effectiveness and cost-utility analysis of LNG-IUS, COC and PROG was carried out using a Markov model based on clinical data from the literature and expert opinion. The population studied were women with a previous diagnosis of idiopathic heavy menstrual bleeding. The analysis was performed from the National Health System perspective, discounting both costs and future effects at 3%. In addition, a sensitivity analysis (univariate and probabilistic) was conducted. RESULTS: The results show that the greater efficacy of LNG-IUS translates into a gain of 1.92 and 3.89 symptom-free months (SFM) after six months of treatment versus COC and PROG, respectively (which represents an increase of 33% and 60% of symptom-free time). Regarding costs, LNG-IUS produces savings of 174.2-309.95 and 230.54-577.61 versus COC and PROG, respectively, after 6 months-5 years. Apart from cost savings and gains in SFM, quality-adjusted life months (QALM) are also favourable to LNG-IUS in all scenarios, with a range of gains between 1 and 2 QALM compared to COC and PROG. CONCLUSIONS: The results indicate that first-line use of the LNG-IUS is the dominant therapeutic option (less costly and more effective) in comparison with first-line use of COC or PROG for the treatment of DUB in Spain. LNG-IUS as first line is also the option that provides greatest health-related quality of life to patients.

Early transjugular intrahepatic portosystemic shunt in cirrhotic patients with acute variceal bleeding: a systematic review and meta-analysis of controlled trials.

INTRODUCTION: There is conflicting evidence on the benefit of early transjugular intrahepatic portosystemic shunt (TIPSS) on the survival of patients with acute variceal bleeding (AVB). AIM: To assess the effect of early TIPSS on patient prognosis. MATERIALS AND METHODS: We carried out a meta-analysis of trials evaluating early TIPSS in cirrhotic patients with AVB. RESULTS: Four studies were included. Early TIPSS was associated with fewer deaths [odds ratio (OR)=0.38, 95% confidence interval (CI)=0.17-0.83, P=0.02], with moderate heterogeneity between studies (P=0.15, I=44%). Early TIPSS was not significantly associated with fewer deaths among Child-Pugh B patients (OR=0.35, 95% CI=0.10-1.17, P=0.087) nor among Child-Pugh C patients (OR=0.34, 95% CI=0.10-1.11, P=0.074). There was no heterogeneity between studies in the Child-Pugh B analysis (P=0.6, I=0%), but there was a high heterogeneity in the Child-Pugh C analysis (P=0.06, I=60%). Early TIPSS was associated with lower rates of bleeding within 1 year (OR=0.08, 95% CI=0.04-0.17, P<0.001) both among Child-Pugh B patients, (OR=0.15, 95% CI=0.05-0.47, P=0.001) and among Child-Pugh C patients (OR=0.05, 95% CI=0.02-0.15, P<0.001), with no heterogeneity between studies. Early TIPSS was not associated with higher rates of encephalopathy (OR=0.84, 95% CI=0.50-1.42, P=0.5). CONCLUSION: Cirrhotic patients with AVB treated with early TIPSS had lower death rates and lower rates of clinically significant bleeding within 1 year compared with patients treated without early TIPSS. Additional studies are required to identify the potential risk factors leading to a poor prognosis after early TIPSS in patients with AVB and to determine the impact of the degree of liver failure on the patient's prognosis.

Self-expandable metal stents in the treatment of acute esophageal variceal bleeding.

Acute variceal bleeding (AVB) is a life-threatening complication in patients with cirrhosis. Hemostatic therapy of AVB includes early administration of vasoactive drugs that should be combined with endoscopic therapy, preferably banding ligation. However, failure to control bleeding or early rebleed within 5 days still occurs in 15-20% of patients with AVB. In these cases, a second endoscopic therapy may be attempted (mild bleeding in a hemodynamically stable patient) or we can use a balloon tamponade as a bridge to definitive derivative treatment (i.e., a transjugular intrahepatic portosystemic shunt). Esophageal balloon tamponade provides initial control in up to 80% of AVB, but it carries a high risk of major complications, especially in cases of long duration of tamponade (>24 h) and when tubes are inserted by inexperienced staff. Preliminary reports suggest that self-expandable covered esophageal metallic stents effectively control refractory AVB (i.e., ongoing bleeding despite pharmacological and endoscopic therapy or massive bleeding precluding endoscopic therapy) with a low incidence of complications. Thus, covered self-expanding metal stents may represent an alternative to the Sengstaken-Blakemore balloon for the temporary control of bleeding in treatment failures. Further studies are required to determine the role of this new device in AVB.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: effect of Anticoagulation and Its Timing: the RAF Study.

BACKGROUND AND PURPOSE: The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. METHODS: The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. RESULTS: Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). CONCLUSIONS: Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.