Higher body weight is associated with lower concentrations of progesterone and estrogen in early pregnancy following in vitro fertilization

To evaluate if body weight impacts progesterone and estradiol concentration levels in early pregnancy in women conceiving following single embryo transfer

Pattern of recurrence in patients with a pathologically complete response after neoadjuvant chemoradiotherapy and surgery for oesophageal cancer

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) and surgery is a widely used treatment for locally advanced resectable oesophageal cancer, with 20-50 per cent of patients having a pathological complete response (pCR). Disease, however, still recurs in 20-30 per cent of these patients. The aim of this study was to assess the pattern of recurrence in patients with a pCR after nCRT and surgery. METHODS: All patients with a pCR after nCRT and surgery included in the phase II and III CROSS (ChemoRadiotherapy for Oesophageal followed by Surgery Study) trials (April 2001 to December 2008) and after the CROSS trials (September 2009 to October 2017) were identified. The site of recurrence was compared with the applied radiation and surgical fields. Outcomes were median time to recurrence, and overall and progression-free survival. RESULTS: A total of 141 patients with a median follow-up of 100 (i.q.r. 64-134) months were included. Some 29 of 141 patients (20,6 per cent) developed recurrence. Of these, four had isolated locoregional recurrence, 15 had distant recurrence only, and ten had both locoregional and distant recurrence. Among the 14 patients with locoregional recurrences, five had recurrence within the radiation field, seven outside the radiation field, and two at the border. Median time to recurrence was 24 (10-62) months. The 5-year overall survival rate was 74 per cent and the recurrence-free survival rate was 70 per cent. CONCLUSION: Despite good overall survival, recurrence still occurred in 21 per cent of patients. Most recurrences were distant, outside the radiation and surgical fields

Characteristics Predicting Short-Term and Long-Term Health-Related Quality of Life in Patients with Esophageal Cancer After Neoadjuvant Chemoradiotherapy and Esophagectomy

Background: Esophagectomy is associated with lasting effect on health-related quality of life (HRQOL). Patients desire detailed information on the expected impact of treatment on their postoperative HRQOL. The aim of the present study is to identify clinicopathological characteristics predictive for changes in short-term and long-term HRQOL after neoadjuvant chemoradiotherapy (nCRT) and surgery. Methods: HRQOL was measured using EORTC-QLQ-C30 and QLQ-OES24 questionnaires prior to nCRT, three, six, nine and twelve months postoperatively and at a minimum of six years postoperatively. Based on previous experience and available literature, several subgroups were predefined for different clinicopathological characteristics: baseline global HRQOL, WHO performance status, histology, tumor stage and tumor location. The primary endpoints of the present study were the change compared to baseline in the HRQOL dimensions physical functioning and eating problems. Secondary endpoints were global HRQOL, fatigue and emotional problems. Results:In total, 134 (76%) of 177 patients who received HRQOL questionnaires, responded at baseline. Patients who reported a high baseline global HRQOL had a more severe deterioration in eating problems (+14.5 to + 18.0), global HRQOL (-16.0 to -28.0) and fatigue (+10.5 to +14.9) up to six years postoperatively compared to patients who reported a low baseline global HRQOL. Patients who had stage 2 tumor (UICC 6th edition) had a more severe deterioration in eating problems (+14.6 to +19.0) and global HRQOL (-10.1 to -17.1) than patients who had stage 3 tumor. Conclusions: The results suggest that patients with locally advanced esophageal cancer in favorable condition at baseline decline more in terms of various HRQOL outcomes.</p

Technological and architectural solutions for Dutch nursing homes:results of a multidisciplinary mind mapping session with professional stakeholders

There is an increasing call in society for the improvement of well-being for nursing home residents and the support of care professionals through a wide array of architectural and technological solutions that are available in modern nursing homes. This study investigated which of these solutions are considered essential by stakeholders from healthcare and technology. Data were gathered via 22 simultaneously held multidisciplinary mind map sessions with 97 stakeholders, resulting in 43 mind maps. These, in turn, were grouped into a single mind map of the nursing home in general, the private rooms for residents with somatic or psychogeriatric health problems, and the group living room. A prioritization of solutions was added. The contents of the mind maps reflect a Dutch consensus on the necessary architectural and technological features for the design of nursing homes.</p

Phase-rectified signal averaging method to predict perinatal outcome in infants with very preterm fetal growth restriction- a secondary analysis of TRUFFLE-trial

BACKGROUND: Phase-rectified signal averaging, an innovative signal processing technique, can be used to investigate quasi-periodic oscillations in noisy, nonstationary signals that are obtained from fetal heart rate. Phase-rectified signal averaging is currently the best method to predict survival after myocardial infarction in adult cardiology. Application of this method to fetal medicine has established significantly better identification than with short-term variation by computerized cardiotocography of growth-restricted fetuses. OBJECTIVE: The aim of this study was to determine the longitudinal progression of phase-rectified signal averaging indices in severely growth-restricted human fetuses and the prognostic accuracy of the technique in relation to perinatal and neurologic outcome. STUDY DESIGN: Raw data from cardiotocography monitoring of 279 human fetuses were obtained from 8 centers that took part in the multicenter European “TRUFFLE” trial on optimal timing of delivery in fetal growth restriction. Average acceleration and deceleration capacities were calculated by phase-rectified signal averaging to establish progression from 5 days to 1 day before delivery and were compared with short-term variation progression. The receiver operating characteristic curves of average acceleration and deceleration capacities and short-term variation were calculated and compared between techniques for short- and intermediate-term outcome. RESULTS: Average acceleration and deceleration capacities and short-term variation showed a progressive decrease in their diagnostic indices of fetal health from the first examination 5 days before delivery to 1 day before delivery. However, this decrease was significant 3 days before delivery for average acceleration and deceleration capacities, but 2 days before delivery for short-term variation. Compared with analysis of changes in short-term variation, analysis of (delta) average acceleration and deceleration capacities better predicted values of Apgar scores <7 and antenatal death (area under the curve for prediction of antenatal death: delta average acceleration capacity, 0.62 [confidence interval, 0.19–1.0]; delta short-term variation, 0.54 [confidence interval, 0.13–0.97]; P=.006; area under the curve for prediction Apgar <7: average deceleration capacity <24 hours before delivery, 0.64 [confidence interval, 0.52–0.76]; short-term variation <24 hours before delivery, 0.53 [confidence interval, 0.40–0.65]; P=.015). Neither phase-rectified signal averaging indices nor short-term variation showed predictive power for developmental disability at 2 years of age (Bayley developmental quotient, <95 or <85). CONCLUSIONS: The phase-rectified signal averaging method seems to be at least as good as short-term variation to monitor progressive deterioration of severely growth-restricted fetuses. Our findings suggest that for short-term outcomes such as Apgar score, phase-rectified signal averaging indices could be an even better test than short-term variation. Overall, our findings confirm the possible value of prospective trials based on phase-rectified signal averaging indices of autonomic nervous system of severely growth-restricted fetuses

Abnormalities in autonomic function in obese boys at-risk for insulin resistance and obstructive sleep apnea.

Study objectivesCurrent evidence in adults suggests that, independent of obesity, obstructive sleep apnea (OSA) can lead to autonomic dysfunction and impaired glucose metabolism, but these relationships are less clear in children. The purpose of this study was to investigate the associations among OSA, glucose metabolism, and daytime autonomic function in obese pediatric subjects.MethodsTwenty-three obese boys participated in: overnight polysomnography; a frequently sampled intravenous glucose tolerance test; and recordings of spontaneous cardiorespiratory data in both the supine (baseline) and standing (sympathetic stimulus) postures.ResultsBaseline systolic blood pressure and reactivity of low-frequency heart rate variability to postural stress correlated with insulin resistance, increased fasting glucose, and reduced beta-cell function, but not OSA severity. Baroreflex sensitivity reactivity was reduced with sleep fragmentation, but only for subjects with low insulin sensitivity and/or low first-phase insulin response to glucose.ConclusionsThese findings suggest that vascular sympathetic activity impairment is more strongly affected by metabolic dysfunction than by OSA severity, while blunted vagal autonomic function associated with sleep fragmentation in OSA is enhanced when metabolic dysfunction is also present

Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer:The Randomized Controlled CROSS Trial

PURPOSE: Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen. METHODS: From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses. RESULTS: The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio [HR], 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent (P value for interaction, P = .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38% v 25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13). CONCLUSION: The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years

Pessaries in multiple pregnancy as a prevention of preterm birth: the ProTwin Trial

Contains fulltext : 79491.pdf (publisher's version ) (Open Access)BACKGROUND: Multiple pregnancies are at high risk for preterm birth, and therefore an important cause of infant mortality and morbidity. A pessary is a simple and potentially effective measure for the prevention of preterm birth. Small studies have indicated its effectiveness, but large studies with sufficient power on the subject are lacking. Despite this lack of evidence, the treatment is at present applied by some gynaecologists in The Netherlands. METHODS/DESIGN: We aim to investigate the hypothesis that prophylactic use of a cervical pessary will be effective in the prevention of preterm delivery and the neonatal mortality and morbidity resulting from preterm delivery in multiple pregnancy. We will evaluate the costs and effects of this intervention. At study entry, cervical length will be measured. Eligible women will be randomly allocated to receive either a cervical pessary or no intervention. The cervical pessary will be placed in situ at 16 to 20 weeks, and will stay in situ up to 36 weeks gestation or until delivery, whatever comes first.The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity). Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 7.2% without to 3.9% with a cervical pessary, using a two-sided test with an alpha of 0.05 and a power of 0.80. DISCUSSION: This trial will provide evidence on whether a cervical pessary will decrease the incidence of early preterm birth and its concomitant bad neonatal outcome in multiple pregnancies. TRIAL REGISTRATION: Current Controlled Trials: NTR 1858

Assessment of perinatal outcome after sustained tocolysis in early labour (APOSTEL-II trial)

Contains fulltext : 80242.pdf (publisher's version ) (Open Access)BACKGROUND: Preterm labour is the main cause of perinatal morbidity and mortality in the Western world. At present, there is evidence that tocolysis for 48 hours is useful in women with threatened preterm labour at least before 32 weeks. This allows transfer of the patient to a perinatal centre, and maximizes the effect of corticosteroids for improved neonatal survival. It is questionable whether treatment with tocolytics should be maintained after 48 hours. METHODS/DESIGN: The APOSTEL II trial is a multicentre placebo-controlled study. Pregnant women admitted for threatened preterm labour who have been treated with 48 hours corticosteroids and tocolysis will be eligible to participate in the trial between 26+0 and 32+2 weeks gestational age. They will be randomly allocated to nifedipine (intervention) or placebo (control) for twelve days or until delivery, whatever comes first.Primary outcome is a composite of perinatal death, and severe neonatal morbidity up to evaluation at 6 months after birth. Secondary outcomes are gestational age at delivery, number of days in neonatal intensive care and total days of the first 6 months out of hospital. In addition a cost-effectiveness analysis will be performed. Analysis will be by intention to treat. The power calculation is based on an expected 11% difference in adverse neonatal outcome. This implies that 406 women have to be randomised (two sided test, beta 0.2 at alpha 0.05). DISCUSSION: This trial will provide evidence as to whether maintenance tocolysis reduces severe perinatal morbidity and mortality in women with threatened preterm labour before 32 weeks. TRIAL REGISTRATION: Clinical trial registration: http://www.trialregister.nl, NTR 1336, date of registration: June 3rd 2008