Monofilament suture versus braided suture thread to improve pregnancy outcomes after vaginal cervical cerclage (C-STICH): a pragmatic randomised, controlled, phase 3, superiority trial.

BACKGROUND: Miscarriage in the second trimester and preterm birth are significant global problems. Vaginal cervical cerclage is performed to prevent pregnancy loss and preterm birth. We aimed to determine the effectiveness of a monofilament suture thread compared with braided suture thread on pregnancy loss rates in women undergoing a cervical cerclage. METHODS: C-STICH was a pragmatic, randomised, controlled, superiority trial done at 75 obstetric units in the UK. Women with a singleton pregnancy who received a vaginal cervical cerclage due to a history of pregnancy loss or premature birth, or if indicated by ultrasound, were centrally randomised (1:1) using minimisation to receive a monofilament suture or braided suture thread for their cervical cerclage. Women and outcome assessors were masked to allocation as far as possible. The primary outcome was pregnancy loss, defined as miscarriage, stillbirth, or neonatal death in the first week of life, analysed in the intention-to-treat population (ie, all women who were randomly assigned). Safety was also assessed in the intention-to-treat population. The trial was registered with ISRCTN, ISRCTN15373349. FINDINGS: Between Aug 21, 2015, and Jan 28, 2021, 2049 women were randomly assigned to receive a monofilament suture (n=1025) or braided suture (n=1024). The primary outcome was ascertained in 1003 women in the monofilament suture group and 993 women in the braided suture group. Pregnancy loss occurred in 80 (8·0%) of 1003 women in the monofilament suture group and 75 (7·6%) of 993 women in the braided suture group (adjusted risk ratio 1·05 [95% CI 0·79 to 1·40]; adjusted risk difference 0·002 [95% CI -0·02 to 0·03]). INTERPRETATION: Monofilament suture did not reduce rate of pregnancy loss when compared with a braided suture. Clinicians should use the results of this trial to facilitate discussions around the choice of suture thread to optimise outcomes. FUNDING: National Institute of Health Research Health Technology Assessment Programme.

A rapid intrapartum test for group B Streptococcus to reduce antibiotic usage in mothers with risk factors: the GBS2 cluster RCT.

BACKGROUND: Mother-to-baby transmission of group B Streptococcus (Streptococcus agalactiae) is the main cause of early-onset infection. OBJECTIVES: We investigated if intrapartum antibiotic prophylaxis directed by a rapid intrapartum test reduces maternal and neonatal antibiotic use, compared with usual care (i.e. risk factor-directed antibiotics), among women with risk factors for vertical group B Streptococcus transmission, and examined the accuracy and cost-effectiveness of the rapid test. DESIGN: An unblinded cluster randomised controlled trial with a nested test accuracy study, an economic evaluation and a microbiology substudy. SETTING: UK maternity units were randomised to either a strategy of rapid test or usual care. PARTICIPANTS: Vaginal and rectal swabs were taken from women with risk factors for vertical group B Streptococcus transmission in established term labour. The accuracy of the GeneXpert® Dx IV GBS rapid testing system (Cepheid, Maurens-Scopont, France) was compared with the standard of selective enrichment culture in diagnosing maternal group B Streptococcus colonisation. MAIN OUTCOME MEASURES: Primary outcomes were rates of intrapartum antibiotic prophylaxis administered to prevent early-onset group B Streptococcus infection and accuracy estimates of the rapid test. Secondary outcomes were maternal antibiotics for any indication, neonatal antibiotic exposure, maternal antibiotic duration, neonatal group B Streptococcus colonisation, maternal and neonatal antibiotic resistance, neonatal morbidity and mortality, and cost-effectiveness of the strategies. RESULTS: Twenty-two maternity units were randomised and 20 were recruited. A total of 722 mothers (749 babies) participated in rapid test units and 906 mothers (951 babies) participated in usual-care units. There were no differences in the rates of intrapartum antibiotic prophylaxis for preventing early-onset group B Streptococcus infection in the rapid test units (41%, 297/716) compared with the usual-care units (36%, 328/906) (risk ratio 1.16, 95% confidence interval 0.83 to 1.64). There were no differences between the groups in intrapartum antibiotic administration for any indication (risk ratio 0.99, 95% confidence interval 0.81 to 1.21). Babies born in the rapid test units were 29% less likely to receive antibiotics (risk ratio 0.71, 95% confidence interval 0.54 to 0.95) than those born in usual-care units. The sensitivity and specificity of the rapid test were 86% (95% confidence interval 81% to 91%) and 89% (95% confidence interval 85% to 92%), respectively. In 14% of women (99/710), the rapid test was invalid or the machine failed to provide a result. In the economic analysis, the rapid test was shown to be both less effective and more costly and, therefore, dominated by usual care. Sensitivity analysis indicated potential lower costs for the rapid test strategy when neonatal costs were included. No serious adverse events were reported. CONCLUSIONS: The Group B Streptococcus 2 (GBS2) trial found no evidence that the rapid test reduces the rates of intrapartum antibiotic prophylaxis administered to prevent early-onset group B Streptococcus infection. The rapid test has the potential to reduce neonatal exposure to antibiotics, but economically is dominated by usual care. The accuracy of the test is within acceptable limits. FUTURE WORK: The role of routine testing for prevention of neonatal infection requires evaluation in a randomised controlled trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN74746075. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 12. See the NIHR Journals Library website for further project information.

WHAT IS THE PROBLEM?: Group B Streptococcus is a common bacterium found in the vagina and intestines of approximately one in four women. Group B Streptococcus may be passed to the baby around birth and cause severe infection. In the UK, women are offered antibiotics in labour to protect their baby from group B Streptococcus infection when specific risk factors are present. Most women with risk factors do not carry group B Streptococcus and their babies are unnecessarily exposed to antibiotics. Most women carrying group B Streptococcus do not have risk factors and so will not be offered antibiotics to protect their babies. WHAT DID WE PLAN TO DO?: We planned to find out if, for women with risk factors, a 'rapid test' in labour resulted in fewer women receiving antibiotics compared with 'usual care'. We also wanted to establish if the test correctly identified if mothers were carrying group B Streptococcus, helped reduce infections in babies and represented value for money. WHAT DID WE FIND?: We involved 1627 women (1700 babies) from 20 hospitals randomly allocated to rapid test or usual care. Using the 'rapid test' did not reduce antibiotics provided to mothers (41% in rapid test units and 36% in usual-care units). The test correctly identified 86% of women carrying group B Streptococcus, 89% of those who did not and failed to provide a result in 14% of women. A rapid test policy resulted in 13% fewer babies receiving antibiotics. The rapid test generated no cost savings when only the mothers' care was considered, but there was potential for reduced costs when including the newborns' hospital stay. WHAT DOES THIS MEAN?: The rapid test is accurate; however, using it for women with risk factors for their baby developing group B Streptococcus infection does not reduce antibiotic usage in mothers, although it does in babies. Value for money is uncertain and depends on what costs are included.

Antimicrobial-impregnated central venous catheters for preventing neonatal bloodstream infection: the PREVAIL RCT.

BACKGROUND: Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies. OBJECTIVES: The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS. DESIGN: Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England. SETTING: The randomised controlled trial was conducted in 18 neonatal intensive care units in England. PARTICIPANTS: Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size). INTERVENTIONS: The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin-miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation. MAIN OUTCOME MEASURE: Study 1 - time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 - cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 - risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data. RESULTS: Study 1, clinical effectiveness - 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter, n = 430; standard peripherally inserted central venous catheter, n = 431). Bloodstream infections occurred in 46 babies (10.7%) randomised to antimicrobial-impregnated peripherally inserted central venous catheters and in 44 (10.2%) babies randomised to standard peripherally inserted central venous catheters. No difference in time to bloodstream infection was detected (hazard ratio 1.11, 95% confidence interval 0.73 to 1.67; p = 0.63). Secondary outcomes of rifampicin resistance in positive blood/cerebrospinal fluid cultures, mortality, clinical outcomes at neonatal unit discharge and time to peripherally inserted central venous catheter removal were similar in both groups. Rifampicin resistance in positive peripherally inserted central venous catheter tip cultures was higher in the antimicrobial-impregnated peripherally inserted central venous catheter group (relative risk 3.51, 95% confidence interval 1.16 to 10.57; p = 0.02) than in the standard peripherally inserted central venous catheter group. Adverse events were similar in both groups. Study 2, economic evaluation - the mean cost of babies' hospital care was £83,473. Antimicrobial-impregnated peripherally inserted central venous catheters were not cost-effective. Given the increased price, compared with standard peripherally inserted central venous catheters, the minimum reduction in risk of bloodstream infection for antimicrobial-impregnated peripherally inserted central venous catheters to be cost-effective was 3% and 15% for babies born at 23-27 and 28-32 weeks' gestation, respectively. Study 3, generalisability analysis - risk-adjusted bloodstream infection rates per 1000 peripherally inserted central venous catheter days were similar among babies in the trial and in all neonatal units. Of all bloodstream infections in babies receiving intensive or high-dependency care in neonatal units, 46% occurred during peripherally inserted central venous catheter days. LIMITATIONS: The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance. CONCLUSIONS: No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin-miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child's life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN81931394. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 57. See the NIHR Journals Library website for further project information.

Babies who are born too early or who are very sick require intensive care after birth and during early life. Most will have a long, narrow, plastic tube, called a catheter, inserted into a vein. The catheter is used to give babies fluids containing medicines and nutrition to keep them well and help them grow. The catheter can remain in place for several days or weeks. But the presence of plastic tubing in the vein increases the risk of infection. This study aimed to find out whether or not catheters coated with antimicrobial medicines, called rifampicin and miconazole, could reduce the risk of infection. These medicines act by stopping germs from growing on the catheter, but do not harm the baby or interfere with other treatments. A randomised controlled trial was carried out in 18 neonatal units in England. Whenever a baby needed a catheter, their parents were asked for consent to participate in the trial. The baby was then randomised, similar to tossing a coin, to receive either the antimicrobial catheter or a standard one. A total of 861 babies participated. We followed up all babies in the same way until after the catheter was removed to compare how often babies in each group had an infection. It was found that antimicrobial catheters were no better or worse at preventing infection than standard catheters. Antimicrobial catheters cost more and we found no evidence of benefit; these results suggest that their use in neonatal intensive care is not justified. It was calculated that further research on ways to reduce infection may be good value for money, depending on the costs of this research. The babies who took part in this study were typical of babies in England receiving catheters, meaning that the results can be applied across the NHS. Future research should focus on catheters that contain other types of antimicrobials and alternative ways of preventing infection.

Antimicrobial-impregnated central venous catheters for prevention of neonatal bloodstream infection (PREVAIL): an open-label, parallel-group, pragmatic, randomised controlled trial.

BACKGROUND: Bloodstream infection is associated with high mortality and serious morbidity in preterm babies. Evidence from clinical trials shows that antimicrobial-impregnated central venous catheters (CVCs) reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is a paucity of similar evidence for babies receiving neonatal intensive care. METHODS: This open-label, parallel-group, pragmatic, randomised controlled trial was done in 18 neonatal intensive care units in England. Newborn babies who needed a peripherally inserted CVC (PICC) were allocated randomly (1:1) to receive either a PICC impregnated with miconazole and rifampicin or a standard (non-antimicrobial-impregnated) PICC. Random allocation was done with a web-based program, which was centrally controlled to ensure allocation concealment. Randomisation sequences were computer-generated in random blocks of two and four, and stratified by site. Masking of clinicians to PICC allocation was impractical because rifampicin caused brown staining of the antimicrobial-impregnated PICC. However, participant inclusion in analyses and occurrence of outcome events were determined following an analysis plan that was specified before individuals saw the unblinded data. The primary outcome was the time from random allocation to first microbiologically confirmed bloodstream or cerebrospinal fluid (CSF) infection between 24 h after randomisation and 48 h after PICC removal or death. We analysed outcome data according to the intention-to-treat principle. We excluded babies for whom a PICC was not inserted from safety analyses, as these analyses were done with groups defined by the PICC used. This trial is registered with ISRCTN, number 81931394. FINDINGS: Between Aug 12, 2015, and Jan 11, 2017, we randomly assigned 861 babies (754 [88%] born before 32 weeks of gestation) to receive an antimicrobial-impregnated PICC (430 babies) or standard PICC (431 babies). The median time to PICC removal was 8·20 days (IQR 4·77-12·13) in the antimicrobial-impregnated PICC group versus 7·86 days (5·00-12·53) days in the standard PICC group (hazard ratio [HR] 1·03, 95% CI 0·89-1·18, p=0·73), with 46 (11%) of 430 babies versus 44 (10%) of 431 babies having a microbiologically confirmed bloodstream or CSF infection. The time from random allocation to first bloodstream or CSF infection was similar between the two groups (HR 1·11, 95% CI 0·73-1·67, p=0·63). Secondary outcomes relating to infection, rifampicin resistance in positive blood or CSF cultures, mortality, clinical outcomes at neonatal unit discharge, and time to PICC removal were similar between the two groups, although rifampicin resistance in positive cultures of PICC tips was higher in the antimicrobial-impregnated PICC group (relative risk 3·51, 95% CI 1·16-10·57, p=0·018). 60 adverse events were reported from 49 (13%) patients in the antimicrobial-impregnated PICC group and 50 events from 45 (10%) babies in the standard PICC group. INTERPRETATION: We found no evidence of benefit or harm associated with miconazole and rifampicin-impregnated PICCs compared with standard PICCs for newborn babies. Future research should focus on other types of antimicrobial impregnation of PICCs and alternative approaches for preventing infection. FUNDING: UK National Institute for Health Research Health Technology Assessment programme.

Universal extraction method for gastrointestinal pathogens.

A universal stool extraction method for recovery of nucleic acids (NAs) from gastrointestinal pathogens was developed to support rapid diagnostics for the London 2012 Olympics. The method involved mechanical disruption (bead beating) of the stools, followed by automated extraction and detection using real-time PCR. This method had been used extensively in the Second Infectious Intestinal Disease Study (IID2) for the isolation of NA from bacteria and parasites (and was effective for the robust recovery of Cryptosporidium spp.) but had not been used for enteric viruses. To ensure this method was universally suitable, panels of samples known to contain target bacteria, viruses or parasites were processed in triplicate using the pre-treatment method routinely used for each target and the new extraction method (bead beating). The extracts were tested using real-time PCR and the cycle threshold values were compared. The results from this study showed that bead beating improved yields for the bacterial and parasitic targets and was suitable for the viral targets. The implementation of this universal method should confer cost- and time-saving benefits and streamline the processes required for the characterization of an array of pathogens from faecal samples.

Survey of access to gastroenterology in Canada: the SAGE wait times program.

BACKGROUND: Assessment of current wait times for specialist health services in Canada is a key method that can assist government and health care providers to plan wisely for future health needs. These data are not readily available. A method to capture wait time data at the time of consultation or procedure has been developed, which should be applicable to other specialist groups and also allows for assessment of wait time trends over intervals of years. METHODS: In November 2008, gastroenterologists across Canada were asked to complete a questionnaire (online or by fax) that included personal demographics and data from one week on at least five consecutive new consultations and five consecutive procedure patients who had not previously undergone a procedure for the same indication. Wait times were collected for 18 primary indications and results were then compared with similar survey data collected in 2005. RESULTS: The longest wait times observed were for screening colonoscopy (201 days) and surveillance of previous colon cancer or polyps (272 days). The shortest wait times were for cancer-likely based on imaging or physical examination (82 days), severe or rapidly progressing dysphagia or odynophagia (83 days), documented iron deficiency anemia (90 days) and dyspepsia with alarm symptoms (99 days). Compared with 2005 data, total wait times in 2008 were lengthened overall (127 days versus 155 days; P<0.05) and for most of the seven individual indications that permitted data comparison. CONCLUSION: Median wait times for gastroenterology services continue to exceed consensus conference recommended targets and have significantly worsened since 2005.

Rotavirus burden among children in the newly independent states of the former union of soviet socialist republics: literature review and first-year results from the rotavirus surveillance network.

BACKGROUND: Data on rotavirus burden among children in the 15 newly independent states of the former Union of Soviet Socialist Republics, particularly contemporary data from poorer countries, are not widely available. These data are desired by policy makers to assess the value of rotavirus vaccination, especially since the GAVI Alliance approved financial support for the region's eligible countries. The Rotavirus Surveillance Network was established to provide these data. METHODS: We reviewed the region's literature on rotavirus burden. We established an active surveillance network for rotavirus and analyzed data from 2007 from 4 sentinel hospitals in 3 countries (Georgia, Tajikistan, and Ukraine) that were collected using standardized enrollment and stool sample testing methods. RESULTS: Specimens for rotavirus testing were collected before 1997 in most studies, and the majority of studies were from 1 country, the Russian Federation. Overall, the studies indicated that approximately 33% of hospitalizations for gastroenteritis among children were attributable to rotavirus. The Rotavirus Surveillance Network documented that 1425 (42%) of 3374 hospitalizations for acute gastroenteritis among children aged <5 years were attributable to rotavirus (site median, 40%). Seasonal peaks (autumn through spring) were observed. Genotype data on 323 samples showed that G1P[8] was the most common type (32%), followed by G9P[8] (20%), G2P[4] (18%), and G4P[8] (18%). Infections due to G10 and G12 and mixed infections were also detected. CONCLUSIONS: The burden of rotavirus disease in the newly independent states is substantial. Vaccines should be considered for disease prevention.

The effects of LIPUS on soft-tissue healing: a review of literature.

INTRODUCTION: Ultrasound is widely used for imaging purposes and as an adjunct to physiotherapy. Low-intensity pulsed ultrasound (LIPUS), having removed the thermal component found at higher intensities, is used to improve bone healing. However, its potential role in soft-tissue healing is still under investigation. MATERIAL AND METHODS: We searched on Medline using the keywords: low-intensity pulsed ultrasound, LIPUS and LIPUS and soft-tissue healing. Thirty-two suitable articles were identified. RESULTS: Research, mainly pre-clinical, so far has shown encouraging result, with LIPUS able to promote healing in various soft tissues such as cartilage, inter-vertebral disc, etc. The effect on the bone-tendon junction, however, is primarily on bone. The role of LIPUS in treating tendinopathies is questionable. Adequately powered human studies with standardisation of intensities and dosages of LIPUS for each target tissue are needed.

Survey of rotavirus surveillance, laboratory capacity and disease burden in the eastern part of the WHO European Region.

Following the licensure of two rotavirus vaccines in Europe, we aimed to assess factors, such as surveillance, disease burden and laboratory capacity, which will be relevant for making decisions about rotavirus vaccine introduction in the different countries. We conducted an email-based survey of the national public health bodies in the World Health Organization (WHO) European Region in 2006 and report here the results from the 23 countries in the eastern part of the region. The survey included questions on rotavirus surveillance, laboratory capacity, burden (in children under the age of five years) and intention to introduce rotavirus vaccination. Countries were grouped into the four per-capita income categories defined by the World Bank. Fourteen of the 23 countries responded to the survey. All except one country reported that less than a quarter of their laboratories had rotavirus diagnostic capacity. Four countries had some form of specific rotavirus surveillance, but half were of very limited coverage. Ten countries did not report data on the incidence of rotavirus hospital admissions, although nine were able to report some data on rotavirus burden. Six of the responding countries said they were likely to introduce universal rotavirus vaccination. Rotavirus surveillance and laboratory capacity in the eastern part of the WHO European Region is limited but most countries had some estimate of rotavirus burden, often from special studies. The reported mortality rates were lower than those from a WHO mortality data source. Many countries in the eastern part of WHO European Region face a number of challenges before vaccine implementation, including strengthening surveillance, improving laboratory capacity and addressing financial barriers.

Detection of viral, bacterial, and parasitological RNA or DNA of nine intestinal pathogens in fecal samples archived as part of the english infectious intestinal disease study: assessment of the stability of target nucleic acid.

Fecal samples were collected from cases and controls as part of the Infectious Intestinal Disease (IID) study in England and were stored as frozen suspensions for 8 to 12 years. The purpose of this study was to apply PCR-based procedures to assess the stability of pathogen-specific nucleic acid sequences present in this archive. Samples from which Cryptosporidium, Giardia, Salmonella, Campylobacter, enteroaggregative Escherichia coli (EAggEC), enterotoxigenic Clostridium perfringens, rotaviruses, noroviruses, or sapoviruses had been previously detected during the IID study using conventional methods were selected from the archive. A generic nucleic acid extraction method to recover RNA or DNA was used. Complementary DNA was generated from RNA by reverse transcription with random priming. Block-based and real-time PCR assays were used to amplify and detect gene fragments from each of these pathogens. The percentage reconfirmation of target was as follows: Giardia duodenalis 68%, Cryptosporidium 96%, Campylobacter 98%, Salmonella 98%, enterotoxigenic C perfringens 34%, EAggEC 93.3%, rotavirus 95%, norovirus 73%, and sapovirus 85%. This study has shown that nucleic acid can be extracted and specific sequences amplified and detected from archived fecal samples. The IID archive therefore represents a valuable resource for further studies, especially the investigation of the samples from which no pathogens had previously been detected.

Incidence and risk factors of paediatric rotavirus diarrhoea in northern Ghana.

We measured the type-specific incidence of paediatric rotavirus diarrhoea in an area of northern Ghana. Over 1 year, diarrhoea 1717 episodes were identified, of which 677 (39%) were positive for rotavirus. Risk factors for rotavirus infection included old age, wasting, high Vesikari score and the episode occurring in the dry season. Rotavirus-positive episodes tended to be more acute, causing vomiting and greater dehydration, and were more likely to require hospitalization. The incidence was 0.089 episodes per person-year for all diarrhoea, and 0.035 for rotavirus diarrhoea. The observed incidence decreased markedly with distance from the nearest health centre, suggesting a large unobserved burden. G2P[6], G3P[4] and G9P[8] made up more than half the genotypes detected, but the remainder were diverse. There is a large burden of rotavirus diarrhoea, but the effectiveness of future vaccines could be diluted by the high polymorphism of the virus, and the difficulty of reaching remote populations.