Mathematically aggregating experts' predictions of possible futures.

Structured protocols offer a transparent and systematic way to elicit and combine/aggregate, probabilistic predictions from multiple experts. These judgements can be aggregated behaviourally or mathematically to derive a final group prediction. Mathematical rules (e.g., weighted linear combinations of judgments) provide an objective approach to aggregation. The quality of this aggregation can be defined in terms of accuracy, calibration and informativeness. These measures can be used to compare different aggregation approaches and help decide on which aggregation produces the "best" final prediction. When experts' performance can be scored on similar questions ahead of time, these scores can be translated into performance-based weights, and a performance-based weighted aggregation can then be used. When this is not possible though, several other aggregation methods, informed by measurable proxies for good performance, can be formulated and compared. Here, we develop a suite of aggregation methods, informed by previous experience and the available literature. We differentially weight our experts' estimates by measures of reasoning, engagement, openness to changing their mind, informativeness, prior knowledge, and extremity, asymmetry or granularity of estimates. Next, we investigate the relative performance of these aggregation methods using three datasets. The main goal of this research is to explore how measures of knowledge and behaviour of individuals can be leveraged to produce a better performing combined group judgment. Although the accuracy, calibration, and informativeness of the majority of methods are very similar, a couple of the aggregation methods consistently distinguish themselves as among the best or worst. Moreover, the majority of methods outperform the usual benchmarks provided by the simple average or the median of estimates.

Listeriosis in pregnancy: under-diagnosis despite over-treatment.

OBJECTIVE: To compare the symptomatology of pregnant women with suspected listeriosis to culture confirmed listeriosis. STUDY DESIGN: All cases of suspected and culture confirmed pregnancy-associated listeriosis from a single center were retrospectively reviewed assessing demographics, clinical, laboratory and pathological findings, and maternal, fetal and neonatal outcomes. RESULTS: Listeriosis was identified in seven patients, none of whom belonged to the 117 women with suspected listeriosis. Women with confirmed infection were more likely to exhibit fever (P=0.01), flu-like symptoms (P=0.006), threatened preterm labor (P=0.05) and inflammatory markers (P=0.02), but less likely to exhibit gastrointestinal complaints (P=0.004) in comparison with suspected non-confirmed cases. Confirmed cases resulted in preterm delivery (n=5) and stillbirth (n=2). Neonatal complications included meningitis, respiratory disease and sepsis. Maternal outcomes were favorable. CONCLUSION: Although 'febrile gastroenteritis' is a poor predictor of listeriosis in pregnancy, fever, premature contractions and inflammatory markers are important risk indices prompting workup and adequate empiric treatment.

The effect of maternal habitus on macronutrient content of human milk colostrum.

OBJECTIVE: There is a paucity of studies on the impact of maternal body mass index (BMI) on macronutrient content of human milk colostrum (HMC). The objective of this study was to compare macronutrient content of HMC in healthy women of term infants in relation to their BMI. We hypothesized that mother habitus influences human milk colostrum content. METHOD: Colostrum was collected from 109 healthy mothers of hospitalized healthy term infants divided into four prepregnancy BMI groups: 12 underweight, 59 normal weight, 20 overweight, and 18 obese women between 24 and 72 h after birth. Macronutrient content was measured using mid-infrared spectroscopy. RESULTS: There were no significant differences in macronutrients between the BMI groups. We performed four separate stepwise backward multiple regression analyses taking into account fat, carbohydrate, protein or energy content as dependent variables and maternal BMI, parity, gestational age, infant gender, maternal age, maternal education, mode of delivery and time postdelivery. In these analyses, fat, carbohydrate and energy content were not related to maternal BMI, while protein content was significantly and positively correlated with BMI (P=0.008) and negatively correlated with gestational age (P=0.004) and time postdelivery (P<0.001). Colostrum carbohydrate content was positively correlated with parity. Colostrum fat and energy content were negatively correlated with maternal age and positively correlated with parity. CONCLUSION: Most macronutrient and energy content of colostrum are unaffected by prepregnancy maternal BMI, with the exception of protein content that is positively related to maternal BMI.

Use of Doppler ultrasound in the management of uteroplacental perfusion during cardiopulmonary bypass in pregnancy.

Cardiopulmonary bypass, the extreme of non-obstetric surgery during pregnancy, presents unique challenges to minimize maternal and fetal risk. We present our experience with a woman who was diagnosed with a left atrial myxoma following an ischemic cerebrovascular accident. We discuss clinical management specific to cardiopulmonary bypass during pregnancy and delivery in the context of a multidisciplinary team approach. We recommend using intermittent Doppler ultrasound as a non-invasive real-time assessment of uteroplacental perfusion during non-obstetric surgery in pregnancy. Monitoring of perfusion facilitates active feedback for appropriate in utero resuscitation in these cases.

The effect of between-breast differences on human milk macronutrients content.

OBJECTIVE: Little is known about the effect of maternal handedness and preferential side of breastfeeding upon macronutrients concentration in human milk (HM). We aimed to compare macronutrients content of HM from both breasts, taking into account the self-reported preferential feeding ('dominant') breast, breast size and handedness (right versus left). We tested the null hypothesis that macronutrients content of HM is not affected by breast dominancy, breast size or maternal handedness. STUDY DESIGN: Fifty-seven lactating mothers were recruited. HM macronutrients were measured after mid manual expression using infrared transmission spectroscopy. RESULTS: Out of the 57 mothers recruited, 12 were excluded from the analyses because they brought in insufficient samples. Among the 22 who reported a size difference, 16 (73%) had a larger left breast (P<0.001). Approximately a third of women reported no breastfeeding side dominance, a third reported a right dominance and another third reported a left dominance. Breastfeeding side dominance was unaffected by either handedness or breasts size. When size asymmetry was reported (n=22) the dominant side was also the larger breast in 16 (73%) women, the smaller breast in 2 (9%) women, whereas 4 (18%) additional women with asymmetry had no preferential breastfeeding side. There were no statistically significant differences in macronutrients between the right and the left breasts. In multiple stepwise backward regression analysis, fat, carbohydrate, protein and energy contents were unaffected by maternal handedness, breast side dominance or breast size asymmetry. CONCLUSIONS: Macronutrients content of mid expression HM is unaffected by maternal handedness, breast size or breast side dominance.

Conservative management of preterm premature rupture of membranes beyond 32 weeks' gestation: is it worthwhile?

We aimed to investigate whether conservative management of preterm premature rupture of membranes (PPROM) at 32-34 weeks' gestation improves outcome. In this retrospective analysis of singleton pregnancies, the study group included patients with PPROM at 28-34 weeks' gestation and the control group included patients presented with spontaneous preterm delivery at 28-34 weeks' gestation. Both groups were subdivided according to gestational age - early (28-31 weeks' gestation) versus late (32-34 weeks' gestation). Adverse neonatal outcome included neonatal death, intraventricular haemorrhage grade 3/4, respiratory distress syndrome, periventricular leucomalacia and neonatal sepsis. The study and control groups included 94 and 86 women, respectively. The study group had a lower incidence of adverse neonatal outcome at the earlier weeks (28-31), compared with the control group at the same gestational age. In contrast, at 32-34 weeks' gestation no difference in the risk for adverse neonatal outcome was noticed. Additionally, within the study group, chorioamnionitis rate was significantly higher among those who delivered at 32-34 weeks' gestation (p < 0.01). No advantage for conservative management of PPROM was demonstrated beyond 31 weeks' gestation. Moreover, conservative management of PPROM at 32-34 weeks' gestation may expose both mother and neonate to infectious morbidity.

The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis.

OBJECTIVE: Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). The pathways affected by tofacitinib and the effects on gene expression in situ are unknown. Therefore, tofacitinib effects on synovial pathobiology were investigated. METHODS: A randomised, double-blind, phase II serial synovial biopsy study (A3921073; NCT00976599) in patients with RA with an inadequate methotrexate response. Patients on background methotrexate received tofacitinib 10 mg twice daily or placebo for 28 days. Synovial biopsies were performed on Days -7 and 28 and analysed by immunoassay or quantitative PCR. Clinical response was determined by disease activity score and European League Against Rheumatism (EULAR) response on Day 28 in A3921073, and at Month 3 in a long-term extension study (A3921024; NCT00413699). RESULTS: Tofacitinib exposure led to EULAR moderate to good responses (11/14 patients), while placebo was ineffective (1/14 patients) on Day 28. Tofacitinib treatment significantly reduced synovial mRNA expression of matrix metalloproteinase (MMP)-1 and MMP-3 (p<0.05) and chemokines CCL2, CXCL10 and CXCL13 (p<0.05). No overall changes were observed in synovial inflammation score or the presence of T cells, B cells or macrophages. Changes in synovial phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT3 strongly correlated with 4-month clinical responses (p<0.002). Tofacitinib significantly decreased plasma CXCL10 (p<0.005) at Day 28 compared with placebo. CONCLUSIONS: Tofacitinib reduces metalloproteinase and interferon-regulated gene expression in rheumatoid synovium, and clinical improvement correlates with reductions in STAT1 and STAT3 phosphorylation. JAK1-mediated interferon and interleukin-6 signalling likely play a key role in the synovial response. TRIAL REGISTRATION NUMBER: NCT00976599.

Breast milk fat content of mothers to small-for-gestational-age infants.

OBJECTIVE: Little is known about the composition of human milk (HM) expressed by mothers of asymmetrically growth-restricted infants. To test the null hypothesis that lactating mothers of small-for-gestational-age (SGA) infants produce milk with fat content similar to that of lactating mothers of infants whose growth is appropriate for gestational age (AGA). STUDY DESIGN: Fifty-six lactating mothers of newborns (26 SGA and 30 AGA) were recruited within the first 3 days of delivery. Creamatocrit (CMT) levels in HM were measured at 72 h, 7 days and 14 days postdelivery in capillary tubes after centrifugation at 9000 r.p.m. for 5 min. RESULT: The groups did not differ in terms of maternal age, body mass index, gestational age (GA), pregnancy weight gain and parity. They differed significantly in terms of infant's birth weight by design. The mean CMT levels at the three time points were similar for the two groups. This remained true when timing of the sample (colostrum, transitional, mature milk) was introduced as a confounder in the analysis of variance (general linear model). CONCLUSION: Fat content of HM is not affected by fetal growth status. We suggest that mothers of SGA infants may be reassured that their milk contains adequate amount of fat that is appropriate for the growth of their infants.

Work disability and productivity loss in patients with inflammatory bowel diseases in Hungary in the era of biologics.

BACKGROUND AND AIMS: To assess work disability (WD) rates in an inflammatory bowel disease (IBD) cohort involving patients with Crohn's disease (CD) or ulcerative colitis (UC) cohort and to identify possible clinical or demographic factors associated with WD. To our knowledge, this is the first study from Eastern Europe that has estimated indirect costs in IBD. METHODS: Data from 443 (M/F: 202/241, CD/UC: 260/183, mean age: 35.5 (CD) and 40.5 (UC) years, biological drug exposure 31.2/11.5%) consecutive patients were included. WD data were collected by questionnaire and the work productivity and activity impairment instrument. Disability pension (DP) rates in the general population were retrieved from public databases. RESULTS: The overall DP rate in this IBD population was 32.3%, with partial disability in 24.2%. Of all DP events, 88.8% were directly related to IBD. Overall, full DP was more prevalent in IBD (RR: 1.51, p < 0.001) and CD (RR: 1.74, p < 0.001) but not in UC compared to the general population and also in CD compared to UC (OR 1.57, p = 0.03). RR for full DP was increased only in young CD patients (RR<35 year olds: 9.4; RR36-40 year olds: 9.4 and 5.6, p < 0.01 for both). In CD, age group, previous surgery, disease duration, frequent relapses, and the presence of arthritis/arthralgia were associated with an increased risk for DP. Among employed patients, absenteeism and presenteeism was reported in of 25.9 and 60.3% patients, respectively, leading to a 28% loss of work productivity and a 32% activity loss, and was associated with disease activity and age group. Average cost of productivity loss due to disability and sick leave with a human capital approach was 1,450 and 430 €/patient/year in IBD, respectively (total productivity loss 1,880 €/patient/year), the costs of presenteeism were 2,605 (SD = 2,770) and 2,410 (SD = 2,970) €/patient/year in CD and UC, respectively. CONCLUSION: Risk of DP was highly increased in young CD patients (sixfold to ninefold). Previous surgery and presence of arthritis/arthralgia was identified as risk factors for DP. Work productivity is significantly impaired in IBD and is associated with high productivity loss.

Major losses of fat, carbohydrates and energy content of preterm human milk frozen at -80°C.

OBJECTIVE: Long-term storage of human milk (HM) requires freezing at low temperatures, the consequences of which upon macronutrients are unclear. To test the null hypothesis that HM freezing and storage for a range of 1 to 10 weeks at -80 °C does not affect HM fat, protein, lactose and energy contents. STUDY DESIGN: Samples of HM were obtained from 20 mothers (60 samples) of preterm infants (25 to 35 weeks gestation), who routinely expressed their milk, every 3 h, using an electric pump, from the second to the seventh week after delivery. All samples were frozen at -80 °C for 8 to 83 days (43.8 days average). After thawing and homogenization, energy and macronutrient contents were measured using an HM analyzer. RESULT: Fat, carbohydrates and energy contents were significantly lower in thawed HM than in fresh HM (fat, fresh vs thawed: 3.72±1.17 vs 3.36±1.19 g/100 ml, P<0.001; carbohydrates, fresh vs thawed: 5.86±0.71 vs 4.09±0.96 g/100 ml, P<0.001; energy, fresh vs thawed: 64.93±12.97 vs 56.63±16.82 kcal/100 ml, P<0.0001), whereas protein content remained unchanged (protein, fresh vs thawed: 1.14±0.36 vs 1.15±0.37 g/100 ml, P=0.7). The decline in carbohydrates content but not in fat and energy correlated significantly with freezing duration. CONCLUSION: Freezing at -80 °C significantly decreases the energy content of HM, both from fat and carbohydrates. Since quantitatively the decrease in macronutrients was much higher than that published for HM storage at -20 °C, our results do not support freezing HM at -80 °C as the gold standard for long-term storage. We suggest that caloric intake calculations in preterm infants cannot be established based upon fresh HM data.

Bach music in preterm infants: no 'Mozart effect' on resting energy expenditure.

OBJECTIVE: To study whether Johan Sebastian Bach music has a lowering effect on resting energy expenditure (REE) similar to that of Wolfgang Amadeus Mozart music. STUDY DESIGN: Prospective, randomized clinical trial with cross-over in 12 healthy, appropriate weights for gestational age (GA), gavage fed, metabolically stable, preterm infants. Infants were randomized to a 30-min period of either Mozart or Bach music or no music over 3 consecutive days. REE was measured every minute by indirect calorimetry. RESULT: Three REE measurements were performed in each of 12 infants at age 20±15.8 days. Mean GA was 30.17±2.44 weeks and mean birthweight was 1246±239 g. REE was similar during the first 10-min of all three randomization periods. During the next 10-min period, infants exposed to music by Mozart had a trend toward lower REE than when not exposed to music. This trend became significant during the third 10-min period. In contrast, music by Bach or no music did not affect significantly REE during the whole study. On average, the effect size of Mozart music upon REE was a reduction of 7.7% from baseline. CONCLUSION: Mozart music significantly lowers REE in preterm infants, whereas Bach music has no similar effect. We speculate that 'Mozart effect' must be taken into account when incorporating music in the therapy of preterm infants, as not all types of music may have similar effects upon REE and growth.

Conclusiveness of the Cochrane reviews in nutrition: a systematic analysis.

BACKGROUND/OBJECTIVE: To assess the conclusiveness of the Cochrane Reviews (CRs) in the field of Nutrition, we tested the hypotheses that: (1) the majority of CRs is inconclusive; (2) the majority of CRs recognizes the need for further and better studies and (3) the ability to reach a conclusion is dependent on the number of studies performed and number of patients enrolled. SUBJECTS/METHODS: We selected all 87 CRs in the field of Nutrition available in Cochrane library. Each CR was analyzed for the number of randomized clinical trials (RCTs) found, number of RCTs included for analysis, number of patients enrolled, the stated need for further studies and the reason(s) for it and the conclusiveness of the CR. RESULTS: Fifty-six out of eighty-seven CRs (64.4%) were conclusive. The average number of available articles, the percentage of articles included, the average number of RCT's retained in the analyses and the total cumulative number of patients enrolled in the studies retained for analysis were significantly higher in conclusive CRs than in non-conclusive ones. The majority of inconclusive CRs (70.9%) recognized the need for further studies, a percentage not significantly different from that found in conclusive ones (58.9%, P=0.26). The percentage of conclusive CRs was not affected by year of publication. CONCLUSIONS: The majority of CRs in Nutrition is conclusive, but most of them emphasize the need for further studies. The ability for a CR to reach a conclusion is affected by the cumulative patient sample size and number of RCT's included in the analysis.

Variety in placental shape: when does it originate?

OBJECTIVES: Observational and empirical evidence suggest that the average placental shape is round with a centrally inserted umbilical cord. Yet variability of shape is common. When in pregnancy do shape and cord insertion variations originate? MATERIALS AND METHODS: Placental measures from published datasets obtained ultrasonographically at 11-14 weeks and/or at term were correlated. RESULTS: Significant correlations were found between the normalized distance of cord insertion to the margin at 11-14 weeks with the same quantity at delivery (r = 0.509, p < 0.0001). First trimester cord marginality was not correlated with two measures of roundness of the delivered placenta (p = 0.448, and p = 0.812). There was a strong correlation between delivered placental thickness and first trimester cord marginality (r = -0.368, p = 0.009). There was a significant relationship between the cord marginality at 11-14 weeks and the mean chorionic vascular density at delivery (r = -0.287, p = 0.015). Placental position in the uterine cavity influences cord marginality at delivery. Modeling suggests that placental growth in the first trimester is non-round. Placental shape at 11-14 weeks is found to be irregular. This irregularity is not correlated with the roundness of the delivered placenta. Both empirically, and in the context of IVF pregnancies, deformation of the vasculogenic zone yields a bi-lobate placental shape. CONCLUSIONS: Our findings strongly support the hypothesis that abnormal cord insertion and a multi-lobate shape result from early influences on the placental growth, such as the shape of the vasculogenic zone, or placental position in the uterus, rather than trophotropism later in pregnancy.

Further assessment of the clinically effective dose range of etoricoxib: a randomized, double-blinded, placebo-controlled trial in rheumatoid arthritis.

OBJECTIVE: To further assess the clinically active dose range of etoricoxib, a COX-2 selective inhibitor, in rheumatoid arthritis (RA). METHODS: RA patients were randomized to etoricoxib 10, 30, 60, or 90 mg or placebo in a double-blind, 12-week study. DMARDs (methotrexate, biologics) or low-dose corticosteroids were allowed in stable doses. The primary endpoint was the proportion of patients completing the study and achieving an American College of Rheumatology 20% (ACR20) response. Secondary endpoints included individual components of the ACR index and Patient Global Assessment of Pain. Safety was assessed by physical exam and adverse experiences (AEs) occurrences. RESULTS: Etoricoxib 90 mg was the only dose to reach a statistically significant difference from placebo (p < 0.001) on the primary endpoint; etoricoxib 60 mg approached significance (p = 0.057). Significant pain improvement vs. placebo was observed with etoricoxib 90 mg (p < 0.001), 60 mg (p = 0.018), and 30 mg (p = 0.017). Despite the use of background biologics and corticosteroids, a dose response was still apparent. A higher proportion of etoricoxib 60 and 90 mg patients had renovascular AEs (i.e., edema and hypertension) compared with placebo, although discontinuations for renovascular AEs were rare. Etoricoxib 90 mg had a higher incidence of serious AEs (n = 5; 1 was considered drug-related) versus placebo (n = 0). LIMITATIONS: The present study was not powered to detect differences in cardiovascular or gastrointestinal safety by dose. Additionally, further research is needed to clarify the role of doses less than the etoricoxib 90 mg dose for pain management in RA patients. CONCLUSION: Etoricoxib 90 mg demonstrated statistically superior efficacy (ACR20) compared with placebo and numerical superiority over the other doses of etoricoxib studied. Etoricoxib 30 and 60 mg demonstrated significant pain improvement versus placebo, suggesting utility for some patients.

Increased cord serum inflammatory markers in small-for-gestational-age neonates.

OBJECTIVE: The pathological picture in ischemic tissue injury shares features with the inflammatory response. Hypoxia-mediated induction of interleukin-6 (IL-6) could set in motion the mechanisms limiting inflammation in ischemia. Intrauterine growth restriction (IUGR) represents a human model of chronic fetal hypoxia. The purpose of this study was a first-time exploration to determine whether cord blood obtained at the delivery of small-for-gestational-age (SGA) infants has increased concentrations of inflammatory markers. STUDY DESIGN: Cord blood was collected from 20 SGA (term and near-term) infants and 20 appropriate-for-gestational-age (AGA) controls. Infants exposed to maternal smoking, diabetes, maternal chronic diseases, or alcohol or drug use were excluded. Both groups had Apgar score ≥7 at 1 min with a normal cord pH (>7.25). Cord-serum cytokines and thrombopoietin (TPO) levels were measured by enzyme linked immunosorbent assay. C-reactive protein (CRP) was measured using a turbidometric immunoassay. RESULT: SGA infants had a significantly smaller birth weight than AGA controls, with a smaller gestation age by 1 week. There were significant elevations in IL-6, tumor necrosis factor (TNF-α), CRP and TPO in the SGA compared with the AGA group, which persisted in multiple regression analysis even after gestational age was taken into account. CONCLUSION: As hypothesized, significant increases in the cord blood concentrations of known inflammatory markers were found in SGA infants compared with the controls.

Denosumab-mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients.

OBJECTIVE: Periarticular osteoporosis is one of the earliest radiographic signs of bone damage in rheumatoid arthritis (RA). Denosumab, an investigational fully human monoclonal antibody that binds to RANKL, inhibits bone erosion and systemic bone loss in clinical studies of patients with RA. In this hand bone mineral density (BMD) substudy, we investigated the effects of denosumab on hand BMD and its correlation with hand erosion scores. METHODS: Patients receiving methotrexate for erosive RA were randomized in a 1:1:1 ratio to receive subcutaneous placebo, denosumab 60 mg, or denosumab 180 mg at 0 and 6 months. Measurements included BMD (by dual x-ray absorptiometry [DXA]) of both hands (0, 1, 6, and 12 months), magnetic resonance images of the hands/wrists (0 and 6 months), and radiographs of the hands/wrists and feet (0, 6, and 12 months). RESULTS: There were 56 patients (13 placebo, 21 denosumab 60 mg, and 22 denosumab 180 mg). Mean changes in hand BMD at 6 and 12 months were: +0.8% and +1.0%, respectively, for denosumab 60 mg; +2.0% and +2.5%, respectively, for denosumab 180 mg; and -1.2% and -2.0%, respectively, for placebo. Erosion scores remained near baseline in the denosumab groups and increased from baseline in the placebo group. A negative correlation was observed between hand BMD and erosion scores. CONCLUSION: In patients with RA, denosumab provided protection against erosion, and not only prevented bone loss but increased hand BMD as measured by DXA.

Prohepcidin concentrations and erythroid progenitors in cord blood of appropriate versus small for gestational age neonates.

OBJECTIVE: Prohepcidin (Pro-Hep), synthesized in the liver, is the prohormone of hepcidin (Hep), which reduces iron absorption in the gut; its synthesis is enhanced by inflammation and is reduced during hypoxia. We aimed to study the hypothesis that infants born small for gestational age (SGA) have reduced cord blood concentrations of Pro-Hep. STUDY DESIGN: Cord blood was collected from 20 SGA (term and near term >35 week gestation) infants and 20 appropriate for gestational age (AGA) controls. We excluded infants exposed to maternal chronic diseases, smoking, diabetes, alcohol or drug use. Both groups had a 1 min Apgar score above or equal to 7 and had normal cord blood pH (above 7.25). ELISA was used to determine serum concentrations of Pro-Hep and erythropoietin (EPO). Circulating CD71(+)/CD45(-)/SSC(low) cells were measured by flow cytometry as an index of erythroid progenitors. RESULT: There were no significant differences between groups in terms of hemoglobin concentrations, and Pro-Hep. In contrast, EPO levels and circulating CD71(+)/CD45(-)/SSC(low) erythroid progenitors were significantly higher in the SGA group. These differences remained significant even after controlling for gestational age and gravidity. CONCLUSION: Contrary to EPO upregulation during intrauterine growth restriction (IUGR), and higher concentrations of circulating erythroid progenitors, Pro-Hep concentration is not affected by IUGR.

Decreased neonatal tibial bone ultrasound velocity in term infants born after breech presentation.

OBJECTIVE: Fetuses found to be in the breech presentation have limited motion of their lower limbs. The aim of this study was to test the hypothesis that bone speed of sound (SOS) would be lower in infants born after breech presentation than in those born after vertex presentation. STUDY DESIGN: We studied 127 singleton, appropriate for gestational age, term infants delivered by a scheduled cesarean delivery at approximately 38 weeks of gestation because of breech presentation or repeat elective cesarean section with vertex presentation. We used the Sunlight Omnisense 7000p device to measure axially transmitted SOS of the right tibia within the first 96 h of life. RESULT: Fifty-three infants studied (42%) were born by cesarean section after breech presentation compared to 74 vertex controls. Bone SOS was significantly lower in the breech presentation group, even after taking into account the effect of gender and parity (as well as gestational age at birth and birth weight). CONCLUSION: Bone SOS is lower in infants born after breech presentation than in those born after vertex presentation. We speculate that limited motion of lower limbs in fetuses found to be in the breech presentation leads to a decrease in bone mineralization and strength.

The immunogenicity, safety, and efficacy of etanercept liquid administered once weekly in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the immunogenicity, safety, and efficacy of 50 mg/mL liquid etanercept. METHODS: In a multicenter, open-label study, adults with active rheumatoid arthritis (RA) received 50 mg/mL liquid etanercept subcutaneously once weekly for 24 weeks. Immunogenicity was assessed at baseline and weeks 24 and 28, safety at all study visits, and efficacy at baseline and weeks 12 and 24. RESULTS: Of 222 treated patients, 88% completed the study; 81% were women; 84% were white; mean age was 53 years; mean RA duration was 10 years. Antibodies to etanercept, all non-neutralizing, were detected in 12 of 214 patients; 7 of the 12 were borderline positive (antibody titers <1:50). The presence of non-neutralizing anti-etanercept antibodies did not appear to affect clinical safety or efficacy. Few patients reported serious adverse events (6.3%), serious infections (2.3%), or withdrew because of adverse events (4.5%). Most adverse events were mild or moderate. The most common event, injection site reaction, occurred in 29.3% patients. At week 24, 63% of patients achieved an ACR20 response, 36% an ACR50 response, and 14% an ACR70 response. Similar responses were apparent by week 12. Week 24 mean improvement in the Health Assessment Questionnaire disability index scores was 0.6 points; improvement in the Short Form-36 Physical Component Score was 10.0 points. CONCLUSION: The 50 mg/mL liquid etanercept formulation administered once weekly was well tolerated. The incidence of anti-etanercept antibodies, the nature and frequency of adverse events, and improvements in signs and symptoms of RA and patient physical function were similar to those in previous etanercept studies.