Cervical pessary versus vaginal progesterone in women with a singleton pregnancy, a short cervix, and no history of spontaneous preterm birth at less than 34 weeks’ gestation: open label, multicentre, randomised, controlled trial

OBJECTIVE To compare the effectiveness of cervical pessary and vaginal progesterone in the prevention of adverse perinatal outcomes and preterm birth in pregnant women of singletons with no prior spontaneous preterm birth at less than 34 weeks’ gestation and who have a short cervix of 35 mm or less. DESIGN Open label, multicentre, randomised, controlled trial. SETTING 20 hospitals and five obstetric ultrasound practices in the Netherlands. PARTICIPANTS Women with a healthy singleton pregnancy and an asymptomatic short cervix of 35 mm or less between 18 and 22 weeks’ gestation were eligible. Exclusion criteria were prior spontaneous preterm birth at less than 34 weeks, a cerclage in situ, maternal age of younger than 18 years, major congenital abnormalities, prior participation in this trial, vaginal blood loss, contractions, cervical length of less than 2 mm or cervical dilatation of 3 cm or more. Sample size was set at 628 participants. INTERVENTIONS 1:1 randomisation to an Arabin cervical pessary or vaginal progesterone 200 mg daily up to 36 weeks’ of gestation or earlier in case of ruptured membranes, signs of infection, or preterm labour besides routine obstetric care. MAIN OUTCOME MEASURES Primary outcome was a composite adverse perinatal outcome. Secondary outcomes were rates of (spontaneous) preterm birth at less than 28, 32, 34, and 37 weeks. A predefined subgroup analysis was planned for cervical length of 25 mm or less. RESULTS From 1 July 2014 to 31 March 2022, 635 participants were randomly assigned to pessary (n=315) or to progesterone (n=320). 612 were included in the intention to treat analysis. The composite adverse perinatal outcome occurred in 19 (6%) of 303 participants with a pessary versus 17 (6%) of 309 in the progesterone group (crude relative risk 1.1 (95% confidence interval (CI) 0.60 to 2.2)). The rates of spontaneous preterm birth were not significantly different between groups. In the subgroup of cervical length of 25 mm or less, spontaneous preterm birth at less than 28 weeks occurred more often after pessary than after progesterone (10/62 (16%) v 3/69 (4%), relative risk 3.7 (95% CI 1.1 to 12.9)) and adverse perinatal outcomes seemed more frequent in the pessary group (15/62 (24%) v 8/69 (12%), relative risk 2.1 (0.95 to 4.6)). CONCLUSIONS In women with a singleton pregnancy with no prior spontaneous preterm birth at less than 34 weeks’ gestation and with a midtrimester short cervix of 35 mm or less, pessary is not better than vaginal progesterone. In the subgroup of a cervical length of 25 mm or less, a pessary seemed less effective in preventing adverse outcomes. Overall, for women with single baby pregnancies, a short cervix, and no prior spontaneous preterm birth less than 34 weeks’ gestation, superiority of a cervical pessary compared with vaginal progesterone to prevent preterm birth and consecutive adverse outcomes could not be proven

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

International audienceBACKGROUND:Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.METHODS:Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.RESULTS:For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, P trend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P trend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98).CONCLUSIONS:These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Background: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] ¼ 0.99, 95% confidence interval [CI] ¼ 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc¼ 0.79, 95% CI ¼ 0.69 to 0.91; HRc¼ 0.70, 95% CI ¼ 0.59 to 0.82; HRc¼ 0.50, 95% CI ¼ 0.40 to 0.63, for 2, 3, and 4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend ¼ .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] ¼ 1.69, 95% CI ¼ 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc ¼ 1.33, 95% CI ¼ 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc¼ 0.72, 95% CI ¼ 0.54 to 0.98). Conclusions: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers

Hoe richt ik onderwijs in voor hoogbegaafde leerlingen en studenten?

Mooij, T., Dijkstra, E., Koper, R., Kester, L., Gijselaers, J., Wolff, Ch., Bahreini, K., De Vries, F., Berkhout, J., & Storm, J. (2012, 20 april). Hoe richt ik onderwijs in voor hoogbegaafden? Masterclass in de OpenU community. Open Universiteit, Heerlen, Nederland. Beschikbaar op http://portal.ou.nl/web/masterclass-hoogbegaafdheid/;Dijkstra, E. M., Mooij, T., & Kirschner, P. A. (2012, 23 April). Excellent Onderwijs en effecten op cognitief excellente leerlingen. Presentation for the Masterclass on education for the gifted, Heerlen, The Netherlands.Tot acht jaar geleden waren er in Nederland vrijwel geen hoogbegaafde leerlingen. Althans, dat werd gezegd in scholen voor primair en voortgezet onderwijs. Statistisch gezien echter was, en is, circa drie procent van hen hoogbegaafd. Incidenteel waren er wel schrijnende beschrijvingen van cognitief hoogbegaafde leerlingen en hun problemen in school. Die beschrijvingen bestaan in Nederland sinds midden jaren tachtig van de vorige eeuw. In het buitenland dateert dat soort informatie al van de jaren '20. Anno 2012 hebben we in scholen, universiteiten en het beleid wel intense aandacht voor excellentie in het onderwijs. Er wordt veel geld besteed aan excellentie. De meest gebruikte definitie van excellentie richt zich op de 10 of 20% best presterenden. Het voordeel daarvan is dat er in elke school en onderwijsinstelling per definitie relatief veel excellente leerlingen, studenten of docenten zijn. Dat geeft houvast, en hoop. Een opvallend punt is echter dat er groot verschil kan zijn tussen hoogbegaafd zijn en excellent zijn. Met name cognitieve hoogbegaafdheid uit zich bij zeer jonge kinderen in vergaande, relatief zelfstandige vorderingen qua taal en rekenen. Als vierjarige functioneren zij soms op het niveau van een leerling in groep 3 of 4. Nog steeds weten scholen hiermee nauwelijks om te gaan. Zij richten hun speel- en leerprocessen in op groepen leerlingen van ongeveer dezelfde leeftijd, met daarop afgestemde materialen en werkwijzen. Die zijn per definitie ongeschikt voor cognitief hoogbegaafden. Vierjarige cognitief hoogbegaafden ervaren dan veelal (gedwongen) onderpresteren, demotivatie en sociale isolatie in groep 1 en 2. De leerkracht neemt dan inderdaad geen hoogbegaafd kind (meer) waar. En, helaas, 10 of 20% best presterenden of 'excellenten' hebben we altijd wel. Maar het zijn dan veelal niet de cognitief hoogbegaafden. De vraag is dan: hoe vergroten we de kans dat een hoogbegaafde leerling ook een excellente leerling is, en blijft? In deze masterclass worden de volgende punten aan de orde gesteld: 1. Waarom zien leerkrachten cognitieve hoogbegaafdheid niet, resp. waarom ondersteunen zij dit niet adequaat wanneer zij dit aanvankelijk wel zien bij een kind in groep 1? 2. Waarom en hoe gaan zij de leerling zien als oorzaak, in plaats van als slachtoffer van gedwongen onderpresteren? 3. Hoe kun je in groep 1 wel een juiste diagnostiek realiseren, gevolgd door een leerpsychologisch verantwoord speel-/leeraanbod? 4. Hoe kun je de organisatie van speel-/leerprocessen in scholen optimaliseren, inclusief de benodigde veranderingen in het team? 5. Hoe trek je de juiste leerpsychologische, onderwijskundige en organisatorische lijnen door in het voortgezet en hoger onderwijs

Systematic review of agents for the management of cancer treatment-related gastrointestinal mucositis and clinical practice guidelines

20Purpose: The aim of this study was to update the clinical practice guidelines for the use of agents for the prevention and/or treatment of gastrointestinal mucositis (GIM). Methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, and No Guideline Possible. Results: A total of 78 papers across 13 interventions were examined of which 25 were included in the final review. No new guidelines were possible for any agent due to inadequate and/or conflicting evidence. Existing guidelines for probiotics and hyperbaric oxygen were unchanged. Conclusions: Of the agents studied for the prevention and treatment of GIM, the evidence continues to support use of probiotics containing Lactobacillus spp. for prevention of chemoradiotherapy and radiotherapy-induced diarrhea in patients with pelvic malignancy, and hyperbaric oxygen therapy to treat radiation-induced proctitis. Additional well-designed research is encouraged to enable a decision regarding palifermin, glutamine, sodium butyrate, and dietary interventions, for the prevention or treatment of GIM.nonenoneBowen J.M.; Gibson R.J.; Coller J.K.; Blijlevens N.; Bossi P.; Al-Dasooqi N.; Bateman E.H.; Chiang K.; de Mooij C.; Mayo B.; Stringer A.M.; Tissing W.; Wardill H.R.; van Sebille Y.Z.A.; Ranna V.; Vaddi A.; Keefe D.M.; Lalla R.V.; Cheng K.K.F.; Elad S.Bowen, J. M.; Gibson, R. J.; Coller, J. K.; Blijlevens, N.; Bossi, P.; Al-Dasooqi, N.; Bateman, E. H.; Chiang, K.; de Mooij, C.; Mayo, B.; Stringer, A. M.; Tissing, W.; Wardill, H. R.; van Sebille, Y. Z. A.; Ranna, V.; Vaddi, A.; Keefe, D. M.; Lalla, R. V.; Cheng, K. K. F.; Elad, S