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To compare the obstetric and perinatal outcomes of deliveries conceived with embryos from single-step vs. sequential culture media systems.Historical cohort of Massachusetts vital records linked to assisted reproductive technology clinic data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System and laboratory embryology data from two large academic hospital fertility centers.Not applicable.Patients with singleton live birth deliveries between 2004 and 2017 conceived with autologous assisted reproductive technology cycles with fresh blastocyst transfer using either single-step (n = 1,058) or sequential (n = 474) culture media systems.None.Associations of single-step vs. sequential culture with obstetric outcomes (mode of delivery, placental abnormalities, pregnancy-induced hypertension, and gestational diabetes) and perinatal outcomes (preterm birth, low birthweight, small-for-gestational-age, and large-for-gestational-age [LGA]) were assessed with multivariate logistic modeling, adjusted for maternal age, race/ethnicity, education, parity, insurance type, protein supplementation, oxygen concentration, fertilization method, and number of transferred embryos.Compared with sequential culture, single-step culture was associated with increased odds of LGA (adjusted odds ratio 2.1, 95% confidence interval 1.04-4.22). There were no statistically significant differences between single-step and sequential culture media systems in the odds of placental abnormalities, pregnancy-induced hypertension, gestational diabetes, prematurity, small-for-gestational-age, or low birthweight.Single-step culture is associated with increased odds of LGA, indicating that embryo culture media systems may affect perinatal outcomes.

Objective To evaluate placenta accreta spectrum with and without placenta previa with regard to risk factors, antepartum diagnosis, and maternal morbidity. Methods We conducted a retrospective cohort study of pathology-confirmed placenta accreta spectrum deliveries with hysterectomy from two U.S. referral centers from January 2010-June 2019. Maternal, pregnancy, and delivery characteristics were compared among placenta accreta spectrum cases with (previa PAS group) and without (nonprevia PAS group) placenta previa. Surgical outcomes and a composite of severe maternal morbidities were evaluated, including eight or more blood cell units transfused, reoperation, pulmonary edema, acute kidney injury, thromboembolism, or death. Logistic regression was used with all analyses controlled for delivery location. Results Of 351 deliveries, 106 (30%) had no placenta previa at delivery. When compared with the previa group, nonprevia placenta accreta spectrum was less likely to be identified antepartum (38%, 95% CI 28-48% vs 87%, 82-91%), less likely to receive care from a multidisciplinary team (41%, 31-51% vs 86%, 81-90%), and less likely to have invasive placenta increta or percreta (51% 41-61% vs 80%, 74-84%). The nonprevia group had more operative hysteroscopy (24%, 16-33% vs 6%, 3-9%) or in vitro fertilization (31%, 22-41% vs 9%, 6-13%) and was less likely to have had a prior cesarean delivery (64%, 54-73% vs 93%, 89-96%) compared with the previa group, though the majority in each group had a prior cesarean delivery. Rates of severe maternal morbidity were similar in the two groups, at 19% (nonprevia) and 20% (previa), even after controlling for confounders (adjusted odds ratio for the nonprevia group 0.59, 95% CI 0.30-1.17). Conclusion Placenta accreta spectrum without previa is less likely to be diagnosed antepartum, potentially missing the opportunity for multidisciplinary team management. Despite the absence of placenta previa and less placental invasion, severe maternal morbidity at delivery was not lower. Broader recognition of patients at risk for placenta accreta spectrum may improve early clinical diagnosis and patient outcomes.

To evaluate whether there are differences in risk factors and maternal outcomes of pregnancies complicated by placenta accreta spectrum depending on the presence or absence of placenta previa.We performed a systematic search in Medline, EMBASE, ClinicalTrials.gov , and Web of Science from inception through April 25, 2022, without language or date restrictions. Search strategy included the key words "placenta accreta," "placenta increta," "placenta percreta," "adherent placenta," "invasive placenta," "abnormal placent*," "placenta previa," and "marginal placent*."Of the 1,122 articles screened, seven studies were included in the final review. Studies were included if they compared the risk factors and maternal outcomes of pregnancies complicated by placenta accreta spectrum depending on the presence or absence of placenta previa.A random-effects model was used to pool the mean differences or odds ratios (OR) and the corresponding 95% CIs using RevMan software. A total of 3,342 pregnancies complicated by placenta accreta spectrum were included in the meta-analysis (2,365 without previa and 977 with previa). Pregnancies complicated by placenta accreta spectrum without previa were more likely to have been conceived by in vitro fertilization (IVF) (OR 3.11, 95% CI 1.93-5.02, P.001, I 2 =52.0%) and to be associated with prior dilation and curettage (DC) (OR 1.60, 95% CI 1.15-2.22, P =.005, I 2 =0.0%) and myomectomy (OR 2.47, 95% CI 1.31-4.66, P =.005, I 2 =0.0%), but they were less likely to be associated with prior cesarean delivery (OR 0.15, 95% CI 0.06-0.37, P.001, I 2 =87.0%). Placenta accreta spectrum without previa was less likely to be diagnosed antenatally (OR 0.07, 95% CI 0.04-0.11, P.001, I 2 =38.0%). Also, women with pregnancies without previa had lower rates of red blood cell transfusion, intensive care unit admission, risk of hysterectomy, unscheduled delivery, and intraoperative bowel or bladder injuries.Pregnancies complicated by placenta accreta spectrum without previa had a more prominent association with IVF and prior DC and myomectomy but were much less likely to be associated with prior cesarean delivery. Further, placenta accreta spectrum without previa was less likely to be diagnosed antenatally, although it had better maternal outcomes as compared with placenta accreta spectrum with previa.PROSPERO, CRD42022307637.

To define specific risk factors for placenta previa in pregnancies conceived with assisted reproductive technology (ART).Retrospective cohort.Fertility centers and inpatient obstetric units in Massachusetts.Patients conceiving with ART and delivering at 20 weeks gestation or later between 2011 and 2017 in Massachusetts.Patient demographic and medical factors and specific components of their cycles. Data were obtained by linking vital records of the State of Massachusetts to reproductive clinic data obtained from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, and then supplementing this information with laboratory and obstetric data from 2 large academic hospitals.Associations were tested between multiple cycle- and patient-related factors and placenta previa or low-lying placenta at delivery. After testing for confounders, multivariate models were adjusted for maternal age, history of prior cesarean delivery and birth plurality, and are reported as adjusted relative risks (aRR).We included 18,939 pregnancies, with 553 (2.9%) having placenta previa at delivery. Advanced maternal age (aRR, 1.25; 95% confidence interval [CI], 1.06-1.48), endometriosis, (aRR, 2.22; 95% CI, 1.71-2.86), and controlled ovarian hyperstimulation (aRR, 1.33; 95% CI, 1.12-1.59) were associated with placenta previa, whereas multiple births (aRR, 0.63; 95% CI, 0.48-0.81) and a history of polycystic ovary syndrome or ovulation disorders (aRR, 0.59; 95% CI, 0.46-0.75) had negative associations. The endometriosis association was strong in nulliparas and the controlled ovarian hyperstimulation association was strong in parous patients in a stratified analysis. No association was seen with prior history of cesarean delivery.Patients conceiving with ART do not have the typical previa risk factors of prior cesarean delivery and multiple gestations, whereas endometriosis and fresh embryo transfers contributed moderate risk. The embryo transfer process itself may affect previa development in this population.

ALTEX - Alternatives to Animal Experimentation Copyright © 2022 the author(s). On April 28-29, 2021, 50 scientists from different fields of expertise met for the 3rd online CIAO workshop. The CIAO project “Modelling the Pathogenesis of COVID-19 using the Adverse Outcome Pathway (AOP) framework” aims at building a holistic assembly of the available scientific knowledge on COVID-19 using the AOP framework. An individual AOP depicts the disease progression from the initial contact with the SARS-CoV-2 virus through biological key events (KE) toward an adverse outcome such as respiratory distress, anosmia or multiorgan failure. Assembling the individual AOPs into a network highlights shared KEs as central biological nodes involved in multiple outcomes observed in COVID-19 patients. During the workshop, the KEs and AOPs established so far by the CIAO members were presented and posi­tioned on a timeline of the disease course. Modulating factors influencing the progression and severity of the disease were also addressed as well as factors beyond purely biological phenomena. CIAO relies on an interdisciplinary crowd­sourcing effort, therefore, approaches to expand the CIAO network by widening the crowd and reaching stakeholders were also discussed. To conclude the workshop, it was decided that the AOPs/KEs will be further consolidated, inte­grating virus variants and long COVID when relevant, while an outreach campaign will be launched to broaden the CIAO scientific crowd. The CIAO project is steered by the Joint Research Centre of the European Commission (EC-JRC), the Humane Society International (HSI), and the Physicians Committee for Responsible Medicine (PCRM). For Jorid Birkelund Sørli, the research is supported by FIKA, Focused Research Effort on Chemicals in the Working Environment from the Danish Government. For Daniel Jacobson, this work was supported by the Laboratory Directed Research and Development Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC for the US Department of Energy (LOIS:10074) and the National Institutes of Health 3RF1AG053303-01S2.

Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver characterized by a complex interaction among genetic factors, immune response to antigens present in hepatocytes, and immune regulation alterations. Its distribution is global and there is a female predominance. AIH is divided into 2 groups, depending on the type of serum autoantibodies detected. The most common presentation is acute hepatitis (40%), with non-specific symptoms, high aminotransferase levels, and hypergammaglobulinemia. Standard treatment consists of the administration of immunosuppressive drugs. It is a complex condition, often difficult to diagnose. If not managed adequately, the 5-year mortality rate may reach 75%.La hepatitis autoinmunitaria es una enfermedad inflamatoria crónica del hígado caracterizada por una interacción compleja entre factores genéticos, respuesta inmunitaria a antígenos presentes en los hepatocitos y alteraciones de la regulación inmunitaria. Presenta una distribución global, con predominio en individuos de sexo femenino. Se clasifica en dos grupos, según el tipo de autoanticuerpos séricos detectados. La forma de presentación más frecuente es la hepatitis aguda (40 %), con síntomas inespecíficos, elevación de aminotransferasas e hipergammaglobulinemia. El tratamiento estándar consiste en la administración de fármacos inmunosupresores. Es una patología compleja, a veces difícil de diagnosticar. Si no se trata de manera adecuada, la mortalidad puede alcanzar el 75 % a los 5 años de evolución.

PURPOSE: To assess the importance of each blastocyst morphological criteria with pregnancy and perinatal outcomes. METHODS: This single-center retrospective cohort study included blastocyst single embryo transfers (SET) performed between 1/2012–2/2018. Poisson regression was used to evaluate pregnancy outcomes following fresh and cryopreserved embryo transfer (CET) for association with blastocyst expansion, inner cell mass (ICM) quality, and trophectoderm (TE) quality. Among cycles resulting in live birth, associations with preterm birth, small for gestational age (SGA) and large for gestational age (LGA), were evaluated using logistic regression. RESULTS: A total of 1023 fresh and 1222 CET cycles were included, of which 465 (45.1%) fresh and 600 (48.5%) CET cycles resulted in singleton live birth. Clinical pregnancy rates increased with increasing expansion among fresh transfers (p for trend = 0.001) but not CET (p = 0.221), and with TE quality for both fresh and CET cycles (p = 0.005 and

PURPOSE: We provide a US national assessment of youth perceptions of the harm and addictiveness of six separate tobacco products, identifying a continuum of perceived harm associated with a range of products in relation to patterns of current use, former use, and susceptibility to use tobacco products. METHODS: We evaluated youth respondents (N = 13,651) ages 12–17 from Wave 1 (2013–2014) of the Population Assessment of Tobacco and Health (PATH) Study. Analyses (2015–2016) focused on refining measures of perceived harm for each product and delineating youth characteristics (demographic, tobacco use status) associated with beliefs about the harmfulness and addictiveness of tobacco products. RESULTS: Cigars, hookah and e-cigarettes were each perceived as having significantly lower harm (p's < 0.05) than smokeless products, with the lowest ratings of harmfulness and addictiveness observed for hookah and e-cigarettes (p's < 0.001). Incrementally lower levels of harm and addictiveness perceptions were observed among youth at increasing risk for tobacco use (p's < 0.05). CONCLUSIONS: Among U.S. youth, lower perceptions of harm and addictiveness of tobacco products were associated with susceptibility to use tobacco and patterns of tobacco product use. Future longitudinal assessments from the PATH Study can provide key information on youth development of perceptions of harm and addictiveness and influences on patterns of tobacco use.

Introduction This study is the first nationally representative survey of U.S. adults (18+) to examine perceptions of the relative harms of eight non-cigarette tobacco products. Methods Data are from Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study Adult Questionnaire, a nationally representative study of 32,320 adults in the United States conducted from September 2013 to December 2014. Results 40.7% of adults believed that electronic cigarettes were less harmful than cigarettes, and 17.8% of adults believed that hookah was less harmful than cigarettes. Those less knowledgeable about the health risks of smoking were more likely to believe that the non-cigarette products were less harmful than cigarettes. Current non-cigarette tobacco product users were more likely to perceive that product to be less harmful than cigarettes (except filtered cigars). There was a significant positive correlation between beliefs that cigarettes were harmful and the likelihood of using hookah; perceptions of the harmfulness of cigarettes was not associated with the likelihood of using any other product. Conclusions Perceptions of harmfulness varied widely across non-cigarette tobacco products. E-cigarettes and hookah in particular are seen as less harmful compared to cigarettes.

The Istituto Superiore di Sanità (ISS) has been asked for rapid technical and scientific advice to the State and Regions during Sars-CoV-2 pandemic preparedness.An ad hoc Working Group on Scientific Literature updates (WG SL) was set up at ISS (March-May 2020) to screen pre-prints and peer reviewed papers from arXiv, medRxiv, bioRxiv, and Pubmed to provide a real time knowledge and empirical evidence addressed to health-workers.The WG SL screened a total of 4,568 pre-prints and 15,590 peer reviewed papers, delivered as daily summary report of pre-print selection for ISS President activity in the National Scientific Technical Committee framework and a weekly open access publication (COVID Contents) on peer-reviewed papers of interest for health professionals, monitored by a satisfaction questionnaire.Promoting heath literacy, with a cross-cutting approach is a powerful heritage of Public Health Institutes and a proven effective non pharmacological intervention.

Luteolin belongs to the family of flavonoids, which have anti-inflammatory functions, potentially useful in a clinical context, particularly for patients suffering from cancer, neuropsychiatric disorders, inflammatory bowel conditions. This peculiarity has been used for centuries in traditional Chinese medicine, for many different diseases. Its anti-inflammatory effects might be particularly relevant in cancer, with some studies reporting anti-angiogenesis, anti-metastatic, and apoptotic effects on cancer cells by luteolin and other flavonoids. In this article, we analyze the anti-inflammatory role of luteolin, discussing the pathways it may act on. We will then discuss the possible role of microbiota in inflammatory modulation by luteolin. Finally, the possible therapeutic applications of luteolin's anti-inflammatory properties will be analyzed, with a particular focus on cancer.

To assess whether placenta accreta spectrum occurs more frequently among women with twin gestations compared with singleton gestations.All live births in California from 2016 to 2017 were identified from previously linked records of birth certificates and birth hospitalization discharges. The primary outcome was placenta accreta spectrum (which includes placenta accreta, increta, and percreta), identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes (O43.2x) for placenta accreta, increta, and percreta. We analyzed the association between twin gestation and placenta accreta spectrum by using multivariable logistic regression and assessed whether our findings were replicated by using a previously validated International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based approach.Among 918,452 live births, 1,126 were diagnosed with placenta accreta spectrum. The prevalence of placenta accreta spectrum was 11.8 per 10,000 among singleton pregnancies and 41.6 per 10,000 among twin pregnancies. In the unadjusted regression analysis, twin pregnancy was associated with higher relative risk of placenta accreta spectrum (RR 3.41, 95% CI 2.57-4.52). After adjusting the regression model for maternal age, previous cesarean birth, and sociodemographic factors, the association held with higher relative risk of placenta accreta spectrum (aRR 2.96, 95% CI 2.23-3.93). Women with twin compared with singleton gestations with placenta accreta spectrum were less likely to have placenta previa. When assessed using ICD-9-CM codes, placenta accreta spectrum was similarly more prevalent among twins than singletons, with an increase in the relative risk of placenta accreta spectrum (aRR 2.45, 95% CI 2.33-3.25).Twin gestation conferred an increased risk for placenta accreta spectrum independent of measured risk factors, which may contribute to increased maternal morbidity in twin gestation compared with singleton gestation. Clinicians should be aware of the increased risk for placenta accreta spectrum in twin gestation and should consider it during ultrasonographic screening.

The role of interleukin (IL)-6 in health and disease has been under a lot of scrutiny in recent years, particularly during the recent COVID-19 pandemic. The inflammatory pathways in which IL-6 is involved are also partly responsible of the development and progression of rheumatoid arthritis (RA), opening interesting perspectives in terms of therapy. Anti-IL-6 drugs are being used with variable degrees of success in other diseases and are being tested in RA. Results have been encouraging, particularly when anti-IL-6 has been used with other drugs, such as metothrexate (MTX). In this review we discuss the main immunologic aspects that make anti-IL-6 a good candidate in RA, but despite the main therapeutic options available to target IL-6, no gold standard treatment has been established so far.

Background: Vaccines are very effective medical tools for disease prevention and life span increase. Controversies have raised concern about their safety, from autism to polio vaccine contamination with simian virus 40 (SV-40). Hysteria surrounding vaccine-associated risks has resulted in a declining number of vaccinations in developed countries. Outbreaks of vaccine-preventable diseases (e.g. measles) have occurred in Europe and North America, causing also some causalities. Objectives: In this review, data on safety and efficacy of vaccines are discussed, showing that the benefits of vaccines far outweigh the risks and that it is important to comply with vaccination protocols, to avoid spreading of severe, preventable diseases. Methods: Those opposed to vaccinations suggest that scientific literature supporting vaccines is influenced by pharmaceutical companies. In this review, studies on influenza produced by independent scientists and those authored by those who received some kind of benefit from the industry are discussed separately. All the chosen papers were selected through a MEDLINE research. Results: Vaccination rates are decreasing, even though they are effective public health tools. Influenza, for example, is responsible for 250,000–500,000 deaths each year, according to the WHO. Yet, campaigns to extend influenza vaccine to all elderly subjects report little success, because of the vaccine scare and because not all patients develop immunity following vaccination. Conclusions: This review proves that vaccine hysteria is detrimental because: 1) it causes an increased morbidity and mortality from preventable diseases; 2) it jeopardizes research for new vaccines; 3) patients are reluctant to accept any form of immune-therapy, commonly referred to as “vaccination”.

Aim Study aimed to analyse how rehabilitation staff spends working time on specific activities in a neurorehabilitation hospital and to determine the number of direct activities received by patients with different levels of disease severity. Background Few studies have investigated how clinical staff spends their time on activities in rehabilitation hospitals without considering at the same time all working categories and without reporting the number of direct activities received by patients with respect to their disease severity. Design Self-reported observational study. Method Work Sampling Technique was used to record direct, indirect, unit-related and personal activities every 5 min for 2 days. Results Total of 6,974 activities were recorded over 581 working hours. Physiotherapists and nurses spent 75.2% and 54.8% of their time in direct activities and medical doctors only 25.4%. Total time of direct activities was significantly different among worker categories (p = 0.001) and depended on patients' disease severity (p = 0.020) in a different manner among worker categories (interaction: p = 0.010). This time ranged from almost 4 hr up to 6½ hr for the most severely affected patients. Conclusion Type of work differed among professionals. Workload greatly depended on degree of patients' disability. Implications for nursing management Nurses and therapists spent most of their time in direct activities with patients. Economic burden of neurorehabilitation may vary greatly depending on disease severity.

Background Hypovolemic hyponatremia has not been widely reported in the obstetric literature. Anecdotally, we noticed severe hyponatremia in several of our patients who presented as home birth transfers, leading to a review of home birth cases and hyponatremia. Given the morbidity associated with hyponatremia, it is important to be aware of its potential occurrence. Case We present the cases of two patients transferred to our hospital with hyponatremia after prolonged labor. These women presented with altered mental status, somnolence, and decreased urine output. Both were admitted to the intensive care unit but made a full recovery. Conclusion Hyponatremia is a serious potential complication of prolonged labor. We propose mechanisms for this condition and recommendations for surveillance and prevention.

Background Brachioplasty is an increasingly performed procedure following massive weight loss. A visible scar is the main hindrance to this surgery. The aims of the study were to develop a physical model to investigate the ideal location of the surgical incision and to present the authors' technical refinements with the posteromedial scar approach. Methods Twenty-four postbariatric patients underwent brachioplasty with posteromedial scar placement, concomitant liposuction, fascial plication, and axillary Z-plasty. Skin specimens were tested and a physical model of the arm was set up to investigate the difference in mechanical stress on the posteromedial and medial scars. The validated Patient and Observer Scar Assessment Scale, the Vancouver Scar Scale, and a questionnaire assessing subjective improvements were administered to patients. Preoperative and postoperative photographs were assessed by three independent plastic surgeons. Results The physical model showed that stress intensity and distribution along the scar were reduced in the posteromedial location, with smaller scar displacement in the loading simulations. Twenty-three patients healed uneventfully. One (4.1 percent) had a 2-cm dehiscence. Mean Patient and Observer Scar Assessment Scale scores were, respectively, 2 ± 0.76 and 2.13 ± 0.64 in the patients' and observers' questionnaires. The mean Vancouver Scar Scale value was 3.5 ± 1.7. Questionnaires assessing the subjective outcomes showed a mean value of 3.45 ± 0.63 of 4. The surgeons' assessment resulted in a score of 4.5 ± 0.4 of 5. Conclusions The physical model demonstrated that the posteromedial scar was subjected to lower mechanical stress and displacement. The reported technical refinements allowed pleasant arm recontouring to be achieved with acceptable scarring and a low incidence of complications. Clinical question/level of evidence Therapeutic, IV.

Background Despite efforts to reduce disadvantages across society, widening health disparities have been observed in Minnesota. This research examined whether observed declines in state-wide smoking prevalence were experienced equally by all adults with varying educational attainment. Methods Serial cross-sectional data from the 2003, 2007, 2010 and 2014 Minnesota Adult Tobacco Survey (MATS) were analyzed. Weighted regression analyses for smoking status, time to first cigarette, cigarettes per day and non-cigarette other tobacco products (OTP) were conducted across education levels. Results Controlling for age and gender, a decreased rate of smoking among high and middle education groups was offset by an increase in the low education group. Dependence (time to first cigarette) was twice as high in the lowest education group compared to highest, yet dependence did not decline over time for any group. There was a decline in cigarettes per day in all education groups, but an increase in OTP use in the lowest and middle education groups. Conclusions Given existing smoking disparities, novel efforts are urgently needed. Complementing known population-level strategies with community and individual-level approaches will be necessary to eliminate the widening gap in smoking disparities and to end the burden of tobacco-related disease.

Postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. While volumetric and gravimetric blood loss measurement techniques have been shown to increase PPH detection compared to visual estimation of blood loss (vBL), a combination of these methods has not been evaluated. The primary aim of this study was to compare the change in odds of PPH detection after vaginal delivery (VD; the intervention series) versus cesarean delivery (CD; the control series) before versus after implementation of a device (Triton LD, Gauss Surgical, Inc, Los Altos, CA) that combines gravimetric and volumetric estimation of blood loss (tBL).After institutional review board (IRB) approval, patients were identified who had a VD or CD at our institution 3 months before and 3 months after the implementation of a tBL device for VD. The levels and trends in odds of PPH detection (the primary outcome, defined as blood loss ≥500 mL for VD and ≥1000 mL for CD) were compared within and between delivery methods before and after implementation of the device. Secondary outcomes were blood loss ≥1000 mL, total blood loss, secondary uterotonic use, and a composite outcome related to PPH management (transfusion, vasopressor administration, and/or surgical procedures). A post hoc subgroup analysis compared nadir hematocrit, hematocrit reduction ≥10%, and difference between vBL or tBL and calculated blood loss (cBL) between VDs before and after introduction of the device. All outcome comparisons were performed using segmented regression with inverse probability of treatment weighting.The weighted odds ratio (wOR) of PPH detection post- versus preimplementation of the device was 2.74 (95% confidence interval [CI], 1.39-5.41; P = .004) for VDs versus 1.43 (95% CI, 0.72-2.85; P = .304) for CDs (P for interaction .190). No difference was detected in the secondary outcomes for VDs between time periods. In the subgroup of VD patients who had postdelivery hematocrits measured, the mean difference between vBL or tBL and cBL was smaller in the tBL (mean ± standard deviation [SD]: -237 ± 522 mL) versus vBL group (-600 ± 596 mL; weighted difference in means [95% CI]: 349 mL [13-684]; P = .042).In this interrupted time series analysis, the odds of PPH detection after VD increased after implementation of the tBL device. However, a statistical difference was not detected between the increase in PPH detection post- versus preimplementation of the device in VDs versus CDs.

In this editorial the authors highlight recent findings which could help design a personalized approach for cancer immunotherapy.

It is now well-known that interleukins (ILs) play a pivotal role in shaping innate immunity: inflammatory ILs are responsible for all innate aspects of immune response, from the very first vascular reactions to the chronic non-specific response to inflammation; while anti-inflammatory ILs are responsible for keeping adaptive immunity at bay. The interactions between ILs and adaptive immunity have been long considered secondary to the effects on the innate immune system, but in recent years it has appeared more clearly that IL direct interactions with adaptive immunity are extremely important both in physiologic and pathologic immune response. In the present review we analyze the role of inflammatory ILs (IL-1, IL-6, IL-33 and IL-37) on adaptive immunity and briefly discuss the possible therapeutic perspectives of IL-blockade in adaptive immunity disorders.

OBJECTIVE: To investigate the relationship between endometriosis and adverse pregnancy outcomes. METHODS: Women between ages 25 and 42 years in 1989 (n=116,429) reported detailed information on pregnancies and reproductive health at baseline and every 2 years thereafter in the Nurses’ Health Study II, a cohort study. In 2009, they completed a detailed, pregnancy-focused questionnaire. A total of 196,722 pregnancies were reported. Adverse pregnancy outcomes included spontaneous abortion, ectopic pregnancy, stillbirth, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (preeclampsia or gestational hypertension), preterm birth, and low birth weight. We estimated the relative risks (RRs) and 95% CIs of adverse pregnancy outcomes comparing pregnancies in women with and without a history of laparoscopically confirmed endometriosis using multivariable log-binomial regression, with generalized estimating equations to account for multiple pregnancies per woman. RESULTS: Endometriosis was associated with a greater risk of pregnancy loss (spontaneous abortion: RR 1.40, 95% CI 1.31–1.49; ectopic pregnancy: RR 1.46, 95% CI 1.19–1.80). Endometriosis was also associated with a greater risk of GDM (RR 1.35, 95% CI 1.11–1.63) and hypertensive disorders of pregnancy (RR 1.30, 95% CI 1.16–1.45). CONCLUSIONS: We observed an association between laparoscopically confirmed endometriosis and several adverse pregnancy outcomes. Future research should focus on the potential biological pathways underlying these relationships to inform screening or preventive interventions.

ObjectiveAnalyze if in utero exposure to economic downturns is associated with worsened birth outcomes.MethodsWe used birth records from all live singleton births in the 27 Brazilian state capitals between October 2012 and December 2016 (n = 2,952,430) and linked them to local unemployment rates according to the mother's residence. We estimated the association between different birth outcomes and the local unemployment rate in the three trimesters before birth. We included maternal characteristics and month, year and municipality fixed effects as covariates. We also estimated the association for different groups of mothers, based on marital status, educational level, age and race.ResultsA 1 p.p. increase in the local unemployment rate in the trimester before birth is associated with 2.68% higher odds of being born with very low birthweight (< 1500 grams) (OR: 1.0268, 95% CI: 1.0006-1.0536). That result is pushed by the effect among newborns from mothers younger than 24 (OR: 1.0684, 95%CI: 1.0353-1.1024), from mothers with 11 years of schooling or less (OR: 1.0477, 95% CI: 1.0245-1.0714), and from brown or black mothers (OR: 1.0387, 95%CI: 1.0156-1.0624). The associations among children born from younger, less educated and black or brown mothers are robust to the application of a procedure to control for multiple testing, albeit the results considering the whole sample are not.ConclusionsOur study shows that there is an association between in utero exposure to higher unemployment rates during the last gestational trimester and the odds of being born with VLBW among children born from mothers younger than 24 years old, with less of 11 years of education and black or brown. These results suggest that children born from women of low socioeconomic status are more vulnerable to in utero exposure to economic downturns.

BACKGROUND Postpartum hemorrhage is a leading source of maternal morbidity and mortality worldwide with uterine atony identified as the underlying cause in up to 80% of cases. Several measures have been utilized to report uterine tone. The most commonly reported measure is a 0 to 10 numeric rating scale, but this scale has not been tested for reliability or agreement between different raters. OBJECTIVE The primary purpose of this study was to evaluate the interrater reliability and agreement of the 0 to 10 visual numeric rating scale of uterine tone during cesarean delivery. A secondary purpose was to obtain estimates of scale responsiveness and minimal clinically important difference. STUDY DESIGN Between August and November of 2018, obstetricians used a 0 to 10 numeric rating score to independently rate uterine tone at 3 and 10 minutes after cesarean delivery by palpation of the uterus. Of note, “0” represented “no tone” and “10” represented excellent tone. Each obstetrician independently and blinded to the other's score pointed to a numeric rating scale held by the anesthesiologist through a clear sterile drape. Intraclass correlation coefficients and Bland-Altman analysis were used to assess interrater reliability and agreement, respectively. Standardized response mean and standard error of measurement were used to obtain estimates of responsiveness and minimal clinically important difference, respectively. RESULTS A total of 82 and 84 pairs of scores were collected at 3 and 10 minutes, respectively, from pairs of 62 unique obstetricians. The mean±standard deviation difference in scores between rater 1 and rater 2 was 0.4±1.4 at 3 minutes and 0.1±1.1 at 10 minutes. Intraclass correlation coefficients for a future single rater (intraclass correlation coefficient [1, 1]) at 3 and 10 minutes were 0.67 (95% confidence interval, 0.53–0.77) and 0.61 (95% confidence interval, 0.46–0.73), and for the average between 2 future raters (intraclass correlation coefficient [1, 2]), they were 0.80 (95% confidence interval, 0.71–0.87) and 0.76 (95% confidence interval, 0.63–0.84), indicating good and excellent reliability, respectively. Bland-Altman analysis estimated 95% limit of agreement between raters of −2.4 (95% confidence interval, −3.0 to −1.9) to 3.1 (95% confidence interval, 2.6–3.7) at 3 minutes and −2.1 (95% confidence interval, −2.5 to −1.7) to 2.4 (95% confidence interval, 2.0–2.8) at 10 minutes, consistent with good interrater agreement at both time points. The standardized response mean from 3 to 10 minutes after delivery was 1.1 (n=81). Standard error of measurement was 1.0 (95% confidence interval, 0.9–1.1) at 3 minutes and 0.8 (95% confidence interval, 0.7–0.9) at 10 minutes. CONCLUSION The 0 to 10 numeric rating scale for uterine tone demonstrated good to excellent interrater reliability with 1 and 2 raters, respectively, and good interrater agreement. The scale was responsive to within-parturient change in tone, and preliminary estimates of the minimal clinically important difference were obtained. The 0 to 10 numeric rating scale for uterine tone may be a reliable, standardized tool for future research in reporting degree of uterotonic contraction during cesarean delivery.

Background This paper describes the methods and conceptual framework for Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study data collection. The National Institutes of Health, through the National Institute on Drug Abuse, is partnering with the Food and Drug Administration9s (FDA) Center for Tobacco Products to conduct the PATH Study under a contract with Westat. Methods The PATH Study is a nationally representative, longitudinal cohort study of 45 971 adults and youth in the USA, aged 12 years and older. Wave 1 was conducted from 12 September 2013 to 15 December 2014 using Audio Computer-Assisted Self-Interviewing to collect information on tobacco-use patterns, risk perceptions and attitudes towards current and newly emerging tobacco products, tobacco initiation, cessation, relapse behaviours and health outcomes. The PATH Study9s design allows for the longitudinal assessment of patterns of use of a spectrum of tobacco products, including initiation, cessation, relapse and transitions between products, as well as factors associated with use patterns. Additionally, the PATH Study collects biospecimens from consenting adults aged 18 years and older and measures biomarkers of exposure and potential harm related to tobacco use. Conclusions The cumulative, population-based data generated over time by the PATH Study will contribute to the evidence base to inform FDA9s regulatory mission under the Family Smoking Prevention and Tobacco Control Act and efforts to reduce the Nation9s burden of tobacco-related death and disease.

A high rate of postoperative complications following inner thigh lift is reported in the medical literature. The authors present the results of a study on the validity of inner thigh contouring, with liposuction and concomitant skin excision, in postbariatric patients.This study examined the charts of 46 postbariatric female patients, who underwent medial thigh lift with a 'T' scar technique and concomitant liposuction, between February 2010 and February 2013. Complications were recorded. A questionnaire was administered to the patients at the 1-year follow-up visit. Preoperative and 1-year postoperative photographs were compared, superimposed, and analysed.This study did not observe major systemic complications, haematoma, seroma, infection, skin necrosis, lymphoceles, or lymphoedema. Minor complications were three cases of wound dehiscence and two cases of deepithelialisation. At the 1-year follow-up visit, caudal scar migration, genital distortion, recurrent ptosis, or deformity of the inner thigh contour were not observed. Questionnaires and a comparison of pre- and 1-year postoperative pictures showed encouraging results.The medial thigh lift technique described and assessed in this article is a straightforward surgical procedure, with considerable functional and aesthetic results. Liposuction, early mobilisation, and appropriate postoperative management are pivotal to reduce postoperative downtime and complications.

Early diagnosis of an extrauterine pregnancy is important for safe and effective management. However, a pregnancy's location often cannot be easily determined with abnormal implantations or prior to 5-6 weeks' gestation. Multiple testing strategies exist to diagnose an abnormal pregnancy when location is unknown, but caution needs to be used to avoid a false diagnosis. Medical treatment is optimal when an abnormal pregnancy is diagnosed early. Because most of these pregnancies are intrauterine, additional testing to localize the pregnancy will allow the correct choice of therapy and avoids unnecessary exposure to a toxic therapy. This testing strategy should be reserved for patients with significant concern for ectopic pregnancy, based on either risk factors or clinical findings. Overuse of this approach can lead to interruption of normal pregnancies.

The placenta accreta spectrum has become an important contributor to severe maternal morbidity. The true incidence is difficult to ascertain, but likely falls near 1/1000 deliveries. This number seems to have increased along with the rate of risk factors. These include placenta previa, previous cesarean section, use of assisted reproductive technologies, uterine surgeries, and advanced maternal age. With increased uterine conservation, previous retained placenta or placenta accreta have become significant risk factors. Understanding placenta accreta spectrum risk factors facilitates patient identification and safe delivery planning. Patients considering elective uterine procedures or delayed childbirth should consider the impact on peripartum morbidity.

To evaluate whether there was an association between the systematic promotion of twin vaginal delivery and an increase in the rates of twin vaginal birth.We conducted a retrospective cohort study. We implemented a quality improvement initiative promoting twin vaginal delivery at an academic tertiary care center in 2013. The program included a needs assessment, simulation of vaginal twin delivery, online educational material, and the expansion of a dedicated twin clinic. We analyzed rates of twin vaginal birth in pregnancies at or beyond 24 weeks of gestation without a contraindication to labor, prior uterine surgery, or a demise or lethal anomaly of either twin. Using linear regression, we calculated annual adjusted rates of twin vaginal birth from 2010 to 2015 and in the 3 years before and after our intervention. We performed an interrupted time-series analysis estimating rates of change before and after the intervention to account for the influence of secular trend.Of 1,574 patients delivering twins, 897 (57%) were included, with 479 in the 3 years before and 418 in the 3 years after the intervention. Adjusted rates of vaginal delivery increased from 32.1% (n=153) to 44.2% (n=185) before and after the intervention (P.01), with a decrease in elective cesarean delivery from 54.6% (n=479) to 44.3% (n=185) (P.01). Rates of breech extraction increased after the intervention (5.7% vs 9.3%, P=.04). However, there was no difference in the rate of change in twin vaginal birth in the time period before (1.35% annual increase, P=.76) or after (5.8% annual increase, P=.40) the intervention.Although we observed an increased rate of twin vaginal birth in the time period after our intervention, because the rates of increase before and after the intervention were not statistically different, the increase is not attributable to our intervention and is more properly attributed to secular trend.

In 2015, the National Partnership for Maternal Safety (NPMS) developed an obstetric hemorrhage consensus bundle to provide birthing facilities in the United States with consistent, validated practice guidelines for postpartum hemorrhage management. The process of implementing each bundle element at a large tertiary labor and delivery unit has not been described; we sought to identify practice deficiencies and perceived barriers to bundle implementation among multidisciplinary providers.We conducted a prospective, cross-sectional, consensus-building study based on the Delphi method. A multidisciplinary expert panel comprised of anesthesiologists, obstetricians, nurses, and surgical technicians was assembled and participated in 4 sequential questionnaires. The first round identified bundle elements that experts determined as not currently adequate and perceived barriers to implementation. The second round established prioritization of elements within each professional group; and the third round ranked the elements with at least 60% agreement on feasibility of implementation and positive impact on patient care. The last round revealed responses across all 4 professional groups to derive a final consensus. Descriptive statistics were performed.A total of 38 experts completed the study (11 anesthesiologists, 11 obstetricians, 10 nurses, and 6 surgical technicians). While all 13 (100%) NPMS obstetric bundle elements were described as deficient in our labor and delivery unit by a provider in at least 1 discipline, consensus among at least 3 of the 4 disciplines was achieved for 6 element deficiencies. Barriers to implementation were determined. The initiatives that achieved consensus as possessing high patient impact and implementation feasibility were protocol-driven management, unit-based simulation drills, blood loss quantification, and team huddles and debriefings.The NPMS obstetric hemorrhage bundle was created to help guide practice and systems improvement for US birthing facilities. The Delphi method enabled identification of deficient elements and perceived barriers to element implementation, as well as group consensus on elements with highest patient impact and feasibility. Multidisciplinary group consensus can identify deficiencies and promote tangible, quality improvements in a large, tertiary-care labor and delivery unit. Institutions may utilize our described technique to guide implementation of future care bundles.

To compare perinatal and peripartum outcomes of vanishing twin gestations with singleton and dichorionic twin gestations in pregnancies conceived by in vitro fertilization.We conducted a retrospective cohort study of vanishing twin pregnancies after fresh and cryopreserved autologous in vitro fertilization cycles performed at our institution from 2007 to 2015. Singleton, dichorionic twin, and dichorionic twin pregnancies with spontaneous reduction to one by 14 weeks of gestation (vanishing twins) were included. Analysis was restricted to patients with a live birth delivery at our institution at or beyond 24 weeks of gestation. The primary outcomes were gestational age and birth weight at delivery; secondary outcomes included peripartum morbidities. A subanalysis further differentiated the vanishing twin pregnancies between those in which demise of the twin occurred before compared with after identification of fetal cardiac activity. Logistic regression models were used to estimate the adjusted odds ratio (OR) with a 95% CI of outcomes.There were 1,189 pregnancies that met inclusion criteria (798 singleton, 291 twin, and 100 vanishing twin). The mean gestational age at birth and birth weights were 38.6±2.3 weeks of gestation and 3,207±644 g in singleton pregnancies, 35.5±2.7 weeks of gestation and 2,539±610 g in twin pregnancies, and 38.5±1.8 weeks of gestation and 3,175±599 g in vanishing twin pregnancies. When compared with twins, those with a vanishing twin had lower odds of preterm delivery (OR 0.13, 95% CI 0.07-0.23; adjusted OR 0.12, 95% CI 0.07-0.22) and small-for-gestational-age birth weight (OR 0.24, 95% CI 0.13-0.45; adjusted OR 0.14, 95% CI 0.07-0.28).In pregnancies conceived by in vitro fertilization that progress to at least 24 weeks of gestation, vanishing twin and singleton pregnancies had similar perinatal and peripartum outcomes. Both were significantly better than twin pregnancies.

© 2018 American Medical Association. All rights reserved. IMPORTANCE Cigarette marketing contributes to initiation of cigarette smoking among young people, which has led to restrictions on use of cigarette advertising. However, little is known about other tobacco advertising and progression to tobacco use in youth and young adults. OBJECTIVE To investigate whether receptivity to tobacco advertising among youth and young adults is associated with progression (being a susceptible never user or ever user) to use of the product advertised, as well as conventional cigarette smoking. DESIGN, SETTING, AND PARTICIPANTS The Population Assessment of Tobacco and Health (PATH) Study at wave 1 (2013-2014) and 1-year follow-up at wave 2 (2014-2015) was conducted in a US population-based sample of never tobacco users aged 12 to 24 years from wave 1 of the PATH Study (N = 10 989). Household interviews using audio computer-assisted self-interviews were conducted. EXPOSURES Advertising for conventional cigarettes, electronic cigarettes (e-cigarettes), cigars, and smokeless tobacco products at wave 1. MAIN OUTCOMES AND MEASURES Progression to susceptibility or ever tobacco use at 1-year follow-up in wave 2. RESULTS Of the 10 989 participants (5410 male [weighted percentage, 48.3%]; 5579 female [weighted percentage, 51.7%]), receptivity to any tobacco advertising at wave 1 was high for those aged 12 to 14 years (44.0%; 95%confidence limit [CL], 42.6%-45.4%) but highest for those aged 18 to 21 years (68.7%; 95%CL, 64.9%-72.2%). e-Cigarette advertising had the highest receptivity among all age groups. For those aged 12 to 17 years, susceptibility to use a product at wave 1 was significantly associated with product use at wave 2 for conventional cigarettes, e-cigarettes, cigars, and smokeless tobacco products. Among committed never users aged 12 to 17 years at wave 1, any receptivity was associated with progression toward use of the product at wave 2 (conventional cigarettes: adjusted odds ratio [AOR], 1.43; 95% CL, 1.23-1.65; e-cigarettes: AOR, 1.62; 95%CL, 1.41-1.85; cigars: AOR, 2.01; 95%CL, 1.62-2.49; and smokeless [males only]: AOR, 1.42; 95%CL, 1.07-1.89) and with use of the product (conventional cigarettes: AOR, 1.54; 95%CL, 1.03-2.32; e-cigarettes: AOR, 1.45; 95%CL, 1.19-1.75; cigars: AOR, 2.07; 95%CL, 1.26-3.40). Compared with those not receptive to any product advertising, receptivity to e-cigarette advertising, but not to cigarette advertising, was independently associated with those aged 12 to 21 years having used a cigarette at wave 2 (AOR, 1.60; 95%CL, 1.08-2.38). CONCLUSIONS AND RELEVANCE Receptivity to tobacco advertisingwas significantly associated with progression toward use in adolescents. Receptivity was highest for e-cigarette advertising and was associated with trying a cigarette.

To evaluate the diagnostic efficacy of contrast enhanced computed tomography (CECT) in emergency departments for diagnosis of necrotizing fasciitis (NF) and for differential diagnosis of other musculoskeletal infections; to correlate radiological findings with the laboratory risk indicator for necrotizing fasciitis (LRINEC).7 radiological parameters to be analysed on CECT scans were established, exams of 36 patients with proven diagnosis of NF (n 12) and other musculoskeletal infections (n 24) were retrospectively reviewed; LRINEC score was calculated. Fisher's test and Spearman's and Kendall's coefficients of rank correlations were performed.Two parameters were found to be strongly associated with the diagnosis of NF: involvement of the fascia (Spearman's ρ of 0.888, p 0.001) and lack of fascial enhancement (Spearman's ρ of 0.672, p 0.001). LRINEC score did not show strong association with the presence of fasciitis NF (Spearman's ρ of 0.490, p = 0.0024).Computed tomography (CT) parameters, which are significantly associated with the diagnosis of NF, are the involvement of the fascia and its lack of enhancement; LRINEC score could be high (5) also in other musculoskeletal infections. Final diagnosis of necrosis among the fascia is surgical. Presence of gas is not a specific sign of necrotizing fasciitis being present in other musculoskeletal infections. CT could easily discriminate NF from other musculoskeletal infections, adds an important value to clinical and laboratory tests in diagnosis of NF in an emergency context when magnetic resonance imaging, which is superior to CT in this discernment, could not be performed.

Both biomedical research and clinical practice rely on complex datasets for the physiological and genetic characterization of human hearts in health and disease. Given the complexity and variety of approaches and recordings, there is now growing recognition of the need to embed computational methods in cardiovascular medicine and science for analysis, integration and prediction. This paper describes a Workshop on Computational Cardiovascular Science that created an international, interdisciplinary and inter-sectorial forum to define the next steps for a human-based approach to disease supported by computational methodologies. The main ideas highlighted were (i) a shift towards human-based methodologies, spurred by advances in new in silico, in vivo, in vitro, and ex vivo techniques and the increasing acknowledgement of the limitations of animal models. (ii) Computational approaches complement, expand, bridge, and integrate in vitro, in vivo, and ex vivo experimental and clinical data and methods, and as such they are an integral part of human-based methodologies in pharmacology and medicine. (iii) The effective implementation of multi- and interdisciplinary approaches, teams, and training combining and integrating computational methods with experimental and clinical approaches across academia, industry, and healthcare settings is a priority. (iv) The human-based cross-disciplinary approach requires experts in specific methodologies and domains, who also have the capacity to communicate and collaborate across disciplines and cross-sector environments. (v) This new translational domain for human-based cardiology and pharmacology requires new partnerships supported financially and institutionally across sectors. Institutional, organizational, and social barriers must be identified, understood and overcome in each specific setting. Both biomedical research and clinical practice rely on complex datasets for the physiological and genetic characterization of human hearts in health and disease. Given the complexity and variety of approaches and recordings, there is now growing recognition of the need to embed computational methods in cardiovascular medicine and science for analysis, integration and prediction. This paper describes a Workshop on Computational Cardiovascular Science that created an international, interdisciplinary and inter-sectorial forum to define the next steps for a human-based approach to disease supported by computational methodologies. The main ideas highlighted were (i) a shift towards humanbased methodologies, spurred by advances in new in silico, in vivo, in vitro, and ex vivo techniques and the increasing acknowledgement of the limitations of animal models. (ii) Computational approaches complement, expand, bridge, and integrate in vitro, in vivo, and ex vivo experimental and clinical data and methods, and as such they are an integral part of human-based methodologies in pharmacology and medicine. (iii) The effective implementation of multi- and interdisciplinary approaches, teams, and training combining and integrating computational methods with experimental and clinical approaches across academia, industry, and healthcare settings is a priority. (iv) The human-based cross-disciplinary approach requires experts in specific methodologies and domains, who also have the capacity to communicate and collaborate across disciplines and cross-sector environments. (v) This new translational domain for human-based cardiology and pharmacology requires new partnerships supported financially and institutionally across sectors. Institutional, organizational, and social barriers must be identified, understood and overcome in each specific setting.

Cardiac CT (CCT) is an imaging modality that is becoming a standard in clinical cardiology. We evaluated indications, safety, and impact on patient management of routine CCT in a multicenter national registry. MATERIALS AND METHODS: During a period of 6 months, 47 centers in Italy enrolled 3,455 patients. RESULTS: CCT was performed mainly with 64-slice CT scanners (73.02 %). Contrast agents were administrated in 3,185 patients (92.5 %). Mean DLP changes with type of scanner and was lower in >64 row detector scanner. The most frequent indication for CCT was suspected CAD (44.8 %), followed by calcium scoring (9.6 %), post-angioplasty/stenting (8.3 %), post-CABGs (7.5 %), study of cardiac anatomy (4.22 %) and assessment in patients with known CAD (4.1 %) and acute chest pain (1.99 %). Most of the CCTs were performed in outpatient settings (2,549; 74 %) and a minority in inpatient settings (719, 20.8 %). Adverse clinical events (mild-moderate) occurred in 26 examinations (0.75 %). None of them was severe. In 45.3 % of the cases CCT findings impacted patient management. CONCLUSION: CCT is performed with different workloads in participating centers. It is a safe procedure and its results have a strong impact on patient management.

OBJECTIVE To identify clinical factors associated with a change from vertex to nonvertex presentation in the second twin after vaginal birth of the first. METHODS We assembled a retrospective cohort of women with viable vertex-vertex twin pregnancies who delivered the presenting twin vaginally. Women whose second twin changed from vertex to nonvertex after vaginal birth of the first were classified as experiencing an intrapartum change in presentation. Characteristics associated with intrapartum presentation change in a univariate analysis with a P value ≤.10 were then evaluated in a multivariate logistic regression model. RESULTS Four-hundred fifty women met inclusion criteria, of whom 55 (12%) had intrapartum presentation change of the second twin. Women experiencing intrapartum presentation change were more likely to be multiparous (69% compared with 47%, P