Outcomes in intervention and management of multiple pregnancies trials: A systematic review.

OBJECTIVES: Twin pregnancy has risks of adverse outcomes for mother and baby. Data synthesis is required to gain evidence to aid recommendations but may be hampered by variations in outcome reporting. STUDY DESIGN: Systematically review outcomes reported in twin pregnancy trials (PROSPERO - CRD42019133805). Searches were performed in MEDLINE, EMBASE, CINHAL, Cochrane library (inception-January 2019) for randomised control trials or their follow-up studies reporting prediction, prognosis, intervention or management outcomes in twin pregnancy. The study characteristics, outcomes definitions and measurements were extracted and descriptively analysed. RESULTS: 49 RCTs and 8 follow-up studies evaluated 21 interventions, 1257 outcomes, categorised into 170 unique outcomes. 65 % of trials included all twin pregnancies, 12 % DCDA and 11 % MCDA only or MCMA and MCDA. Five (9 %) papers were prediction/ prognosis RCT's and 52 (91 %) related to an intervention. Of interventions, 40 (77 %) were medical, 34 (85 %) for preterm birth; 12 (23 %) surgical, 6 (50 %) related to TTTS interventions (83 % for monochrorionic studies). Commonest domains were: 'Neonatal' 77 %, 'Delivery' 70 % and 'Survival' 67 %. Least reported were longer term outcomes for 'Infant' or 'Parental'. CONCLUSIONS: Twin pregnancy outcomes are diverse and complex. This is related to the need to address maternal, single and double fetal outcomes and different types of chorionicity. The lack of outcome standardisation in selection, definition and reporting hinders evidence synthesis and the selection of outcomes important to women and health care professionals thus limiting the effectiveness of research.

Vaginal preparation with chlorhexidine at cesarean section to reduce endometritis and prevent sepsis: A randomized pilot trial (PREPS).

INTRODUCTION: Cesarean sections are the most common major operation worldwide. One in 10 women develops a surgical-site infection after cesarean section. The PREPS pilot trial was developed to assess the feasibility of a randomized controlled trial of vaginal cleansing with chlorhexidine before cesarean section, to reduce infectious morbidity. MATERIAL AND METHODS: A multi-center, open-label, parallel-group pilot randomized controlled trial across 4 UK maternity units. Women aged ≥16 years, undergoing elective or emergency cesarean section, ≥34 weeks of gestation, and able to give informed consent were eligible. Women were randomized 1:1 to chlorhexidine 0.05% or no cleansing and were followed up until 6 weeks after cesarean section. The feasibility of a larger randomized controlled trial was assessed by the pilot trial's recruitment, ability to use verbal consent in an emergency, adherence, follow-up and withdrawal rates. The main clinical outcome collected was Center for Disease Control and Prevention (CDC) classification of endometritis at 30 days. Trial registration number is ISRCTN33435996. RESULTS: A total of 320 women (128% of target) were randomized. Of these, 93% (95% CI 89%-95%) received their allocated intervention. Of the 88 women who had an emergency cesarean section, verbal consent was initially given by 32 (36%) women, with the remainder having sufficient time to give written consent. Endometritis (CDC definition) was collected from medical notes of 96% of women, 68% (95% CI 63%-73%) were followed up at both 14 and 30 days by telephone, and we were able to collect patient-reported outcomes. In the vaginal cleansing arm 2/152 (1.3%) women had endometritis compared with 1/155 (0.7%) in the no cleansing arm (RR 2.08, 95% CI 0.19-22.31). CONCLUSIONS: It is possible to perform a randomized controlled trial in women undergoing an elective or emergency cesarean section, using a verbal-followed-by-written consent process, while maintaining high adherence and retaining women in the trial.

Are prophylactic adjunctive macrolides efficacious against caesarean section surgical site infection: A systematic review and meta-analysis.

Surgical site infection (SSI) post- caesarean section (CS) remains high, prophylactic adjunctive macrolides may reduce this. This systematic review and meta-analysis evaluated whether adjunctive prophylactic macrolides administered at CS reduce the risk of endometritis and wound infection. MEDLINE, EMBASE, CINHAL and the Cochrane library were searched from inception to July-2018. Observational and randomised studies investigating women undergoing a CS receiving standard prophylactic antibiotics, adjunctive prophylactic macrolides and assessed any SSI outcome was included. Data was double-extracted. Studies were included in a meta-analysis if the same study design and SSI outcome was used. Risk ratios were calculated and heterogeneity was assessed using the I2 test. Five studies were included in the systematic review and four in the meta-analysis. Two RCT's (n = 2610) found that macrolides significantly reduce the risk of wound infection RR [0.34; 95 %, 0.22 0.53] P = 0.00001 and endometritis RR [0.66; 95 %, 0.52, 0.85] P = 0.001 with no evidence of heterogeneity (I2 = 0 %). Two cohort studies (n = 13,809) found that azithromycin significantly reduces the risk of endometritis RR [0.16; 95 %, 0.04-0.62] P = 0.008, however significant heterogeneity was seen. Macrolides significantly reduce the risk of endometritis and wound infection post-CS. An effectiveness evaluation of post-cord clamping administration is needed to eliminate fetal antibiotic exposure and the long term infant implications this may have.

Women's perspectives on caesarean section recovery, infection and the PREPS trial: a qualitative pilot study.

BACKGROUND: In England, 27.8% of all pregnant women undergo caesarean sections (CS) to deliver their babies. Women undergoing CS are at risk of developing sepsis and post-natal infections, which not only contribute significantly to maternal mortality and morbidity, but also negatively impact upon post-natal recovery and wellbeing. This study explores patients' priorities in relation to CS recovery, focusing on their knowledge and experiences of infection prevention. The study formed part of the PREPS (Vaginal Preparation at caesarean section to Reduce Endometritis and Prevent Sepsis - a feasibility study of chlorhexidine) Trial; patients' views on the PREPS Trial were also sought. METHODS: Using qualitative methodology, two focus groups and six telephone interviews were carried out between September and October 2017 with a total of 21 women who had undergone a CS within the preceding six months. Focus groups and individual telephone interviews were audio-recorded and transcribed verbatim; a thematic analysis was conducted using NVivo 11. RESULTS: Women's priorities around CS recovery centred on pain (or the lack thereof), mobility and the ability to resume everyday activities, including caregiving. Those undergoing a CS for the first time reported not feeling confident in their ability to identify signs of infection and sought visiting health professionals' expertise and reassurance. Women were unable to recall whether they had received information regarding infection prevention and felt that they had not received sufficient advice. Some reported receiving general information regarding CS recovery, which ranged in quality. Prevention of womb infection is a major goal of the PREPS trial, however, the majority of women were not aware that womb (as opposed to wound) infection was a post CS risk. CONCLUSIONS: Women undergoing a CS want more information on what constitutes a 'normal' post-operative recovery and specifically would welcome written information and infection prevention advice. This should be a key element of improving post-CS maternal experiences and potentially reducing sepsis and infection rates. CS stigma negatively impacts women's recovery experiences and possibly information provision. The PREPS team incorporated findings regarding consent pathways for recruiting women into intrapartum research and developed two patient reported outcomes to collect in the main trial. TRIAL REGISTRATION: The PREPS trial has been registered with ISRCTN on the 10th July 2017 ( ISRCTN33435996 ).

Stable isotope profiling of burnt wooden safety matches.

Arson is a significant problem around the world, and is a crime which results in a low number of convictions. The scene of an arson can be varied, commercial, residential or national park, and recently cases have been identified which were initiated by a lit match. Matches can be recovered from a scene, usually in a burnt condition. The benefit of analysing unburnt matches has been researched previously. In most cases, burnt matches are recovered from scenes, and therefore the research was extended to investigate the potential of using IRMS to analyse burnt matches. This includes samples which have been exposed to petrol, and various fire extinguishing chemicals. Matches were sectioned to reveal central unburnt portions of wood and analysed by isotope ratio mass spectrometry (IRMS). The stable isotope profile (SIP) of the wooden matchstick samples was unaffected by the presence of both petrol and a variety of fire extinguisher chemicals. Any changes seen could be attributed to the natural variability of isotopic composition encountered in a natural material such as wood. These findings were confirmed by the isotope analysis of 19 matchstick samples placed in mock fire training scenarios. The data was examined using a paired t-test and Hotellings T2 test for a single sample.

Urea unfolding of opsin in phospholipid bicelles.

Opsin is the unstable apo-protein of the light-activated G protein-coupled receptor rhodopsin. We investigated the stability of bovine opsin, solubilized in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/detergent bicelles, against urea-induced unfolding. A single irreversible protein unfolding transition was observed from changes in intrinsic tryptophan fluorescence and far-UV circular dichroism. This unfolding transition correlated with loss of protein activity. Changes in tertiary structure, as indicated by fluorescence measurements, were concomitant with an approximate 50% reduction in alpha-helical content of opsin, indicating that global unfolding had been induced by urea. The urea concentration at the midpoint of unfolding was dependent on the lipid/detergent environment, occurring at approximately 1.2 m urea in DMPC/1,2-dihexanoyl-sn-glycero-3-phosphocholine bicelles, while being significantly stabilized to approximately 3.5 m urea in DMPC/3-[(cholamidopropyl)dimethylammonio]-1-propanesulfonate bicelles. These findings demonstrate that interactions with the surrounding lipids and detergent are highly influential in the unfolding of membrane protein structure. The urea/bicelle system offers the possibility for a more detailed understanding of the structural changes that take place upon irreversible unfolding of opsin.

Opsin stability and folding: modulation by phospholipid bicelles.

Integral membrane proteins do not fare well when extracted from biological membranes and are unstable or lose activity in detergents commonly used for structure and function investigations. We show that phospholipid bicelles provide a valuable means of preserving alpha-helical membrane proteins in vitro by supplying a soluble lipid bilayer fragment. Both 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)/3-[(cholamidopropyl)dimethyl-ammonio]-1-propane sulfonate (Chaps) and DMPC/l-alpha-1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) bicelles dramatically increase the stability of the mammalian vision receptor rhodopsin as well as its apoprotein, opsin. Opsin is particularly unstable in detergent solution but can be directly purified into DMPC/Chaps. We show that opsin can also be directly purified in DMPC/DHPC bicelles to give correctly folded functional opsin, as shown by the ability to regenerate rhodopsin to approximately 70% yield. These well-characterised DMPC/DHPC bicelles enable us to probe the influence of bicelle properties on opsin stability. These bicelles are thought to provide DMPC bilayer fragments with most DHPC capping the bilayer edge, giving a soluble bilayer disc. Opsin stability is shown to be modulated by the q value, the ratio of DMPC to DHPC, which reflects changes in the bicelle size and, thus, proportion of DMPC bilayer present. The observed changes in stability also correlate with loss of opsin secondary structure as determined by synchrotron far-UV circular dichroism spectroscopy; the most stable bicelle results in the least helix loss. The inclusion of Chaps rather than DHPC in the DMPC/Chaps bicelles, however, imparts the greatest stability. This suggests that it is not just the DMPC bilayer fragment in the bicelles that stabilises the protein, but that Chaps provides additional stability either through direct interaction with the protein or by altering the DMPC/Chaps bilayer properties within the bicelle. The significant stability enhancements and preservation of secondary structure reported here in bicelles are pertinent to other membrane proteins, notably G-protein-coupled receptors, which are unstable in detergent solution.

Stable hydrogen isotope ratios of lignin methoxyl groups as a paleoclimate proxy and constraint of the geographical origin of wood.

Stable isotope ratios of organic compounds are valuable tools for determining the geographical origin, identity, authenticity or history of samples from a vast range of sources such as sediments, plants and animals, including humans. Hydrogen isotope ratios (delta(2)H values) of methoxyl groups in lignin from wood of trees grown in different geographical areas were measured using compound-specific pyrolysis isotope ratio mass spectrometry analysis. Lignin methoxyl groups were depleted in (2)H relative to both meteoric water and whole wood. A high correlation (r(2) = 0.91) was observed between the delta(2)H values of the methoxyl groups and meteoric water, with a relatively uniform fractionation of -216 +/- 19 per thousand recorded with respect to meteoric water over a range of delta(2)H values from -110 in northern Norway to +20 per thousand in Yemen. Thus, woods from northern latitudes can be clearly distinguished from those from tropical regions. By contrast, the delta(2)H values of bulk wood were only relatively poorly correlated (r(2) = 0.47) with those of meteoric water. Measurement of the delta(2)H values of lignin methoxyl groups is potentially a powerful tool that could be of use not only in the constraint of the geographical origin of lignified material but also in paleoclimate, food authenticity and forensic investigations.

Kinetics of an individual transmembrane helix during bacteriorhodopsin folding.

The kinetics of an individual helix of bacteriorhodopsin have been monitored during folding of the protein into lipid bilayer vesicles. A fluorescence probe was introduced at individual sites throughout helix D of bacteriorhodopsin and the changes in the fluorescence of the label were time-resolved. Partially denatured, labelled bacteriorhodopsin in SDS was folded directly into phosphatidylcholine lipid vesicles. Stopped-flow mixing of the reactants allowed the folding kinetics to be monitored with millisecond time resolution by time-resolving changes in the label fluorescence, intrinsic protein fluorescence as well as in the absorption of the retinal chromophore. Monitoring specific positions on helix D showed that two kinetic phases were altered compared to those determined by monitoring the average protein behaviour. These two phases, of 6.7 s(-1) and 0.33 s(-1), were previously assigned to formation of a key apoprotein intermediate during bacteriorhodopsin folding. The faster 6.7s(-1) phase was missing when time-resolving fluorescence changes of labels attached to the middle of helix D. The amplitude of the 0.33 s(-1) phase increased along the helix, as single labels were attached in turn from the cytoplasmic to the extracellular side. An interpretation of these results is that the 6.7 s(-1) phase involves partitioning of helix D within the lipid headgroups of the bilayer vesicle, while the 0.33 s(-1) phase could reflect transmembrane insertion of this helix. In addition, a single site on helix G was monitored during folding. The results indicate that, unlike helix D, the insertion of helix G cannot be differentiated from the average protein behaviour. The data show that, while folding of bacteriorhodopsin from SDS into lipids is a co-operative process, it is nevertheless possible to obtain information on specific regions of a membrane protein during folding in vitro.