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

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Informed consent procedures in patients with an acute inability to provide informed consent

Purpose: Enrolling traumatic brain injury (TBI) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice. Methods: Variation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries. Results: Variation in the use of informed consent procedur

Is nephrocalcinosis in preterm neonates harmful for long-term blood pressure and renal function?

OBJECTIVE. The aim of our study was to examine long-term effects of nephrocalcinosis in prematurely born children. PATIENTS AND METHODS. Preterm neonates (gestational age < 32 weeks) with (n=42) and without (n=32) nephrocalcinosis were prospectively studied at a mean age of 7.5 (+/- 1.0) years. RESULTS. Blood pressure did not differ in ex- preterm infants with and without nephrocalcinosis but was significantly higher than expected for healthy children. In comparison to healthy children, more ex- preterm infants with neonatal nephrocalcinosis had (mild) chronic renal insufficiency (glomerular filtration rate: < 85 mL/ min per 1.73 m(2); 6 of 40); this is in contrast to ex- preterm infants without neonatal nephrocalcinosis (2 of 32). Tubular phosphate reabsorption and plasma bicarbonate were significantly lower in children with nephrocalcinosis compared with children without nephrocalcinosis. In addition, more ex- preterm infants with and without nephrocalcinosis than expected had low values for plasma bicarbonate and early- morning urine osmolality compared with healthy children. Kidney length of ex- preterm infants with and without nephrocalcinosis was significantly smaller than expected in healthy children of the same height. Nephrocalcinosis persisted long- term in 4 of 42 children but was not related to blood pressure, kidney length, or renal function. CONCLUSIONS. Nephrocalcinosis in preterm neonates can have long- term sequelae for glomerular and tubular function. Furthermore, prematurity per se is associated with high blood pressure, relatively small kidneys, and (distal) tubular dysfunction. Long-term follow-up of blood pressure and renal glomerular and tubular function of preterm neonates, especially with neonatal nephrocalcinosis, seems warranted

Long-Term Neurodevelopmental and Functional Outcomes of Infants Born Very Preterm and/or with a Very Low Birth Weight

Background: Birth weight (BW) is often used as a proxy for gestational age (GA) in studies on preterm birth. Recent findings indicate that, in addition to perinatal outcomes, subjects born very preterm (VP; GA <32 weeks) differ from those with a very low birth weight (VLBW; BW <1,500 g) in postnatal growth up to their final height. Objective: To study whether neurodevelopmental and functional outcomes at the age of 19 years differ in VP and/or VLBW subjects. Methods: 705 19-year-old subjects from the Project on Preterm and Small-for-Gestational-Age Infants (POPS) cohort were classified as (1) VP+/VLBW+ (n = 354), (2) VP+/VLBW-(n = 144), or (3) VP-/VLBW+ (n = 207), and compared with regard to IQ as assessed with the Multicultural Capacity Test-intermediate level; neuromotor function using Touwen's examination of mild neurologic dysfunction; hearing loss; self-and parent-reported behavioral and emotional functioning; educational achievement and occupation; and self-assessed health using the Health Utilities Index and the London Handicap Scale. Results: VP+/VLBW-infants, on average, had 3.8-point higher IQ scores (95% confidence interval [CI] 0.57.1), a trend towards higher educational achievement, 3.3dB better hearing (95% CI 1.2-5.4), and less anxious behavior, attention problems, and internalizing behavior than to VP+/VLBW+ subjects. VP-/VLBW+ infants reported 1.8 increased odds (95% CI 1.2-2.6) of poor health compared to VP+/VLBW+ subjects. Conclusions: At the age of 19 years, subjects born VP+/VLBW+, VP+/VLBW-, and VP-/VLBW+ have different neurodevelopmental and functional outcomes, although effect sizes are small. Hence, the terms VP and VLBW are not interchangeable. We recommend, at least for industrialized countries, to base inclusion in future studies on preterm populations on GA instead of on BW. (c) 2018 The Author(s) Published by S. Karger AG, Base

No association between transient hypothyroxinemia of prematurity and neurodevelopmental outcome in young adulthood

Context: Transient hypothyroxinemia of prematurity (THoP) has been associated with neurodevelopmental impairment in infancy and childhood. It is not known whether these relations persist into adulthood. Objective: The objective was to examine whether there is an effect of THoP on intelligence quotient (IQ) score and motor functioning at a young adult age. Design: This study was part of the 19-year follow-up of the Project On Preterm and Small-forgestational-age birth (POPS) cohort, which included infants born very preterm (ie,32 wk) and/or with a very low birth weight (ie, 1500 g). Setting: This was a multicenter study. Patients: There were 398 19-year-old participants of the POPS cohort, of whom 120 had THoP. Exposure: T4 concentrations were obtained through the national neonatal screening program for congenital hypothyroidism.THoP was defined as a total T4 concentration< -3 SD of the daily mean (approximately 60 nmol/L). Main Outcome Measures: Main outcome measures were IQ and motor functioning, measured with the digital Multicultural Capacities Test-Intermediate Level and a revised version of Touwen’s examination of minor neurological dysfunction, respectively. Results: THoP was not associated with IQ score (mean difference, 0 [95% confidence interval,3.8 to 3.8] points) or motor function (mean difference, 0.6 [95% confidence interval, 1.3 to 2.5] points) after adjustment for demographic and perinatal characteristics. Conclusions: No associations between THoP and neurodevelopmental outcome at age 19 years were found

No association between transient hypothyroxinemia of prematurity and neurodevelopmental outcome in young adulthood

\u3cp\u3eContext: Transient hypothyroxinemia of prematurity (THoP) has been associated with neurodevelopmental impairment in infancy and childhood. It is not known whether these relations persist into adulthood. Objective:Theobjectivewastoexaminewhetherthere isaneffect ofTHoPonintelligence quotient (IQ) score and motor functioning at a young adult age. Design: This study was part of the 19-year follow-up of the Project On Preterm and Small-forgestational-age birth (POPS) cohort, which included infants born very preterm (ie,&lt;32 wk) and/or with a very low birth weight (ie, &lt;1500 g). Setting: This was a multicenter study. Patients: There were 398 19-year-old participants of the POPS cohort, of whom 120 had THoP. Exposure: T\u3csub\u3e4\u3c/sub\u3e concentrations were obtained through the national neonatal screening program for congenital hypothyroidism.THoPwasdefined as a total T\u3csub\u3e4\u3c/sub\u3e concentration &lt;-3 SDof the dailymean (approximately 60 nmol/L). Main Outcome Measures: Main outcome measures were IQ and motor functioning, measured with the digital Multicultural Capacities Test-Intermediate Level and a revised version of Touwen's examination of minor neurological dysfunction, respectively. Results: THoP was not associated with IQ score (mean difference, 0 [95% confidence interval,-3.8 to 3.8] points) or motor function (mean difference, 0.6 [95% confidence interval, -1.3 to 2.5] points) after adjustment for demographic and perinatal characteristics. Conclusions: No associations between THoP and neurodevelopmental outcome at age 19 years were found.\u3c/p\u3