Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Pregnancy in women with portal vein thrombosis: Results of a multicentric European study on maternal and fetal management and outcome

Background & Aims: Women of childbearing age account for approximately 25% of patients with non-cirrhotic portal vein thrombosis (PVT). We aimed at assessing maternal and fetal outcome in pregnant women with known PVT. Methods: We performed a retrospective analysis of the files of women with chronic PVT in three European referral centers between 1986 and 2010. Results: Forty-five pregnancies, 28 (62%) treated with low molecular weight heparin, occurred in 24 women. Nine (20%) were lost before gestation week 20. Preterm birth occurred in 38% of deliveries: there were 3 births at week 24-25, 7 at week 32-36, and 26 after week 37. A term birth with a healthy infant occurred in 58% of pregnancies. Cesarean section was used in 53% of deliveries. Two women developed HELLP syndrome. A favorable outcome happened in 64% of pregnancies. Pregnancies with an unfa Conclusions: In pregnant PVT patients treated with anticoagulation on an individual basis, the rate of miscarriage and preterm birth appears to be increased. However, fetal and maternal outcomes are favorable for most pregnancies reaching gestation week 20. High platelet counts appear to increase the risk for unfavorable outcome. Pregnancy should not be contraindicated in stable PVT patients. (C) 2012 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver

Therapeutic and other interventions to reduce the risk of mother-to-child transmission of HIV-1 in Europe. The European Collaborative Study

C. Thorne, M.-L. Newell, A. Bailey, C.S. Peckham, C. Giaquinto, E. Ruga, A. De Rossi, D. Truscia, I. Grosch-Worner, A. Schafer, J. Mok, F. Johnstone, F. Omenaca, J. Jiminez, C.De Alba, M.C. Garcia-Rodriguez, I. Bates, I. De Jose, F. Hawkins, R. Martinez Zapico, F. Asensi-Botet, M.C. Otero, D. Perez-Tamarit, A. Gonzalez Molina, H. Canosa, H. Scherpbier, K. Boer, A.B. Bohlin, S. Lindgren, E. Belfrage, J. Levy, A. Alimenti, P. Barlow, A. Ferrazin, A. Dre Maria, C. Gotta, V. Maritati, A. Mur, M.T. Rovira, A. Paya, O. Coll, C. Fortuny, J. Boguna, M. Casellas Caro, Y. Canet, G. Pardi, A.E. Semprini, M. Ravizza, C. Castagna, S. Fiore, B. Guerra, S. Bianchi, L. Bovicelli, E. Prati, S. Zanelli, M. Duse, A. Soresina, G. Scaravelli, M. Stegagno, M. De Santis, M.-L. Muggiasca, P. Marchisio, A. Iasci, A. Spinillo, A. Bucceri, E. Grossi, L. Rancilio, R. Smith, A.-M. Lewi

Combination antiretroviral therapy and duration of pregnancy

Objective: To assess the association between type and timing of initiation of antiretroviral therapy in pregnancy and duration of pregnancy. Design: Prospective study. Methods: Data on 3920 mother child pairs were examined (3015 mother-child pairs from the European Collaborative Study and 905 from the Swiss Mother + Child HIV Cohort Study). Factors examined included gestational age, antiretroviral therapy during pregnancy, maternal CD4 count, viral load, illicit drug use (IDU) and mode of delivery. Deliveries at less than 37 weeks were defined as premature. Results: The prematurity rate was 17% and median gestational age 39 weeks. Twenty-three per cent (896 of 3920) of women received antiretroviral therapy during pregnancy: 64% (573 of 896) zidovudine monotherapy, 24% (215) combination therapy without protease inhibitors (PI) and 12% (108) combination therapy with PI. In multivariate analysis, adjusted for maternal CD4 count and IDU, odds ratio (OR) of prematurity was 2.60 195% confidence interval (CI), 1.43-4.751 and 1.82 (95% CI, 1.13-2.92) for infants exposed to combination therapy with and without a Pl, respectively, compared to no treatment. Exposure to monotherapy was not associated with prematurity, but severe immunosuppression and IDU in pregnancy were. Women on combination therapy from before pregnancy were twice as likely to deliver prematurely as those starting therapy in the third trimester (OR, 2.17 95% CI, 1.03-4.58). Conclusions: Pregnancy issues should be discussed when making decisions about initiation of combination antiretroviral therapy for HIV-infected women. Elective caesarean section to reduce vertical transmission at 36 weeks rather than 38 weeks may be advisable in women on combination therapy with PI. © 2000 Lippincott Williams & Wilkins

Duration of ruptured membranes and vertical transmission of HIV-1: A meta-analysis from 15 prospective cohort studies

Objective: To test the a priori hypothesis that longer duration of ruptured membranes is associated with increased risk of vertical transmission of HIV. Design: The relationship between duration of ruptured membranes and vertical transmission of HIV was evaluated in an individual patient data meta-analysis. Methods: Eligible studies were prospective cohort studies including at least 100 mother-child pairs, from regions where HIV-infected women are counselled not to breastfeed. Analyses were restricted to vaginal deliveries and non-elective Cesarean sections; elective Cesarean section deliveries (those performed before onset of labour and before rupture of membranes) were excluded. Results: The primary analysis included 4721 deliveries with duration of ruptured membranes ≤ 24 h. After adjusting for other factors known to be associated with vertical transmission using logistic regression analysis to assess the strength of the relationship, the risk of vertical HIV transmission increased approximately 2% with an increase of 1 h in the duration of ruptured membranes [adjusted odds ratio, 1.02; 95% confidence interval, 1.01-1.04; for each 1 h increment]. There were no significant interactions of duration of ruptured membranes with study cohort or with any of the covariates, except maternal AIDS. Among women diagnosed with AIDS, the estimated probability of transmission increased from 8% to 31% with duration of ruptured membranes of 2 h and 24 h respectively (P < 0.01). Conclusions: These results support the importance of duration of ruptured membranes as a risk factor for vertical transmission of HIV and suggest that a diagnosis of AIDS in the mother at the time of delivery may potentiate the effect of duration of ruptured membranes. © 2001 Lippincott Williams & Wilkins

The Mode Of Delivery And The Risk Of Vertical Transmission Of Human Immunodeficiency Virus Type 1. A Meta-Analysis Of 15 Prospective Cohort Studies

Background To evaluate the relation between elective cesarean section and vertical transmission of human immunodeficiency virus type 1 (HIV-1), we performed a meta-analysis using data on individual patients from 15 prospective cohort studies. Methods North American and European studies of at least 100 mother-child pairs were included in the meta-analysis. Uniform definitions of modes of delivery were used. Elective cesarean sections were defined as those performed before onset of labor and rupture of membranes. Multivariate logistic-regression analysis was used to adjust for other factors known to be associated with vertical transmission. Results The primary analysis included data on 8533 mother-child pairs. After adjustment for receipt of antiretroviral therapy, maternal stage of disease, and infant birth weight, the likelihood of vertical transmission of HIV-1 was decreased by approximately 50 percent with elective cesarean section, as compared with other modes of delivery (adjusted odds ratio, 0.43; 95 percent confidence interval, 0.33 to 0.56). The results were similar when the study population was limited to those with rupture of membranes shortly before delivery. The likelihood of transmission was reduced by approximately 87 percent with both elective cesarean section and receipt of antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, as compared with other modes of delivery and the absence of therapy (adjusted odds ratio, 0.13; 95 percent confidence interval, 0.09 to 0.19), Among mother-child pairs receiving antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, rates of vertical transmission were 2.0 percent among the 196 mothers who underwent elective cesarean section and 7.3 percent among the 1255 mothers with other modes of delivery. Conclusions The results of this meta-analysis suggest that elective cesarean section reduces the risk of transmission of HIV-1 from mother to child independently of the effects of treatment with zidovudine. (N Engl J Med 1999;340:977-87.) (C)1999, Massachusetts Medical Society