Prophylactic antibiotics in the prevention of infection after operative vaginal delivery (ANODE): a multicentre randomised controlled trial.

BACKGROUND: Risk factors for maternal infection are clearly recognised, including caesarean section and operative vaginal birth. Antibiotic prophylaxis at caesarean section is widely recommended because there is clear systematic review evidence that it reduces incidence of maternal infection. Current WHO guidelines do not recommend routine antibiotic prophylaxis for women undergoing operative vaginal birth because of insufficient evidence of effectiveness. We aimed to investigate whether antibiotic prophylaxis prevented maternal infection after operative vaginal birth. METHODS: In a blinded, randomised controlled trial done at 27 UK obstetric units, women (aged ≥16 years) were allocated to receive a single dose of intravenous amoxicillin and clavulanic acid or placebo (saline) following operative vaginal birth at 36 weeks gestation or later. The primary outcome was confirmed or suspected maternal infection within 6 weeks of delivery defined by a new prescription of antibiotics for specific indications, confirmed systemic infection on culture, or endometritis. We did an intention-to-treat analysis. This trial is registered with ISRCTN, number 11166984, and is closed to accrual. FINDINGS: Between March 13, 2016, and June 13, 2018, 3427 women were randomly assigned to treatment: 1719 to amoxicillin and clavulanic acid, and 1708 to placebo. Seven women withdrew, leaving 1715 in the amoxicillin and clavulanic acid group and 1705 in the placebo groups. Primary outcome data were missing for 195 (6%) women. Significantly fewer women allocated to amoxicillin and clavulanic acid had a confirmed or suspected infection (180 [11%] of 1619) than women allocated to placebo (306 [19%] of 1606; risk ratio 0·58, 95% CI 0·49-0·69; p<0·0001). One woman in the placebo group reported a skin rash and two women in the amoxicillin and clavulanic acid reported other allergic reactions, one of which was reported as a serious adverse event. Two other serious adverse events were reported, neither was considered causally related to the treatment. INTERPRETATION: This trial shows benefit of a single dose of prophylactic antibiotic after operative vaginal birth and guidance from WHO and other national organisations should be changed to reflect this. FUNDING: NIHR Health Technology Assessment programme

The views of older women towards mammographic screening: a qualitative and quantitative study

Purpose: Mammographic screening has improved breast cancer survival in the screened age group. This improved survival has not been seen in older women (>70 years) where screening uptake is low. This study explores the views, knowledge and attitudes of older women towards screening. Methods: Women (>70) were interviewed about breast screening. Interview findings informed the development of a questionnaire which was sent to 1000 women (>70) to quantify their views regarding screening. Results: Twenty-six women were interviewed and a questionnaire designed. The questionnaire response rate was 48.3% (479/992). Over half (52.9%, 241/456) of respondents were unaware they could request mammography by voluntary self-referral and were unaware of how to arrange this. Most (81.5% 383/470) had not attended breast screening since turning 70. Most (75.6%, 343/454) felt screening was beneficial and would attend if invited. Most, (90.1%, 412/457) felt screening should be offered to all women regardless of age or health. Conclusions: There is a lack of knowledge about screening in older women. The majority felt that invitation to screening should be extended to the older age group regardless of age or health. The current under-utilised system of voluntary self referral is not supported by older women

Hand Preference Develops Across Childhood and Adolescence in Extremely Preterm Children: The EPICure Study.

AIM: To determine how handedness changes with age and its relation to brain injury and cognition following birth before 26 weeks of gestation. METHODS: We used data from the EPICure study of health and development following birth in the British Isles in 1995. Handedness was determined by direct observation during standardized testing at age 2.5, six, and 11 years and by self-report using the Edinburgh Handedness Inventory at 19 years. Control data from term births were included at six, 11, and 19 years. RESULTS: In extremely preterm children left handedness increased from 9% to 27% between 2.5 and 19 years, with a progressive reduction in mixed handedness from 59% to 13%. Although individual handedness scores varied over childhood, the between-group effects were consistent through 19 years, with greatest differences in females. In extremely preterm participants, neonatal brain injury was associated with lower right handedness scores at each age and left-handed participants had lower cognitive scores at 19 years after controlling for confounders, but not at other ages. CONCLUSION: Increasing hand lateralization is seen over childhood in extremely preterm survivors, but consistently more have non-right preferences at each age than controls

Recognition of cancer warning signs and anticipated time to help-seeking in a population sample of adults in the UK

Background: Not recognising a symptom as suspicious is a common reason given by cancer patients for delayed help-seeking; but inevitably this is retrospective. We therefore investigated associations between recognition of warning signs for breast, colorectal and lung cancer and anticipated time to help-seeking for symptoms of each cancer. Methods: Computer-assisted telephone interviews were conducted with a population-representative sample (N=6965) of UK adults age greater than or equal to50 years, using the Awareness and Beliefs about Cancer scale. Anticipated time to help-seeking for persistent cough, rectal bleeding and breast changes was categorised as >2 vs less than or equal to2 weeks. Recognition of persistent cough, unexplained bleeding and unexplained lump as cancer warning signs was assessed (yes/no). Associations between recognition and help-seeking were examined for each symptom controlling for demographics and perceived ease of health-care access. Results: For each symptom, the odds of waiting for >2 weeks were significantly increased in those who did not recognise the related warning sign: breast changes: OR=2.45, 95% CI 1.47–4.08; rectal bleeding: OR=1.77, 1.36–2.30; persistent cough: OR=1.30, 1.17–1.46, independent of demographics and health-care access. Conclusion: Recognition of warning signs was associated with anticipating faster help-seeking for potential symptoms of cancer. Strategies to improve recognition are likely to facilitate earlier diagnosis

Time spent in primary care for hip osteoarthritis patients once the diagnosis is set: a prospective observational study

Background: Previous research on time to referral to orthopaedic surgery has predominantly used hip complaints as starting point instead of the moment the diagnosis of osteoarthritis (OA) of the hip is established, therefore little is known about the length of time a patient diagnosed with hip OA stays under the care of a general practitioner (GP). No knowledge on factors of influence on this time period is available either. Aim of this study was thus to determine the time an incident hip OA patient stays in the care of a GP until referral to an orthopaedic department. Influencing factors were also analyzed. Methods: A prospective observational study was conducted based on data over a 10-year period from a general practice-based registration network (17 GPs, > 30,000 patients registered yearly). Patients with the diagnosis of hip OA were included. A survival analysis was used to determine time until referral to an orthopaedic department, and to determine factors of influence on this time. Results: Of 391 patients diagnosed with hip OA, 121 (31%) were referred; average survival time until referral was 82.0 months (95% CI 76.6-87.5). Less contact with the GP for hip complaints before the diagnosis of hip OA was established resulted in a decreased time to referral. Conclusions: The results of this study show that patients with hip OA were under the care of a general practitioner, and thus in primary care, for a considerable amount of time once the diagnosis of hip OA was established

Annual consultation prevalence of regional musculoskeletal problems in primary care: an observational study

<p>Abstract</p> <p>Background</p> <p>Regional musculoskeletal pain such as back or shoulder pain are commonly reported symptoms in the community. The extent of consultation to primary care with such problems is unknown as a variety of labels may be used to record such consultations. The objective was to classify musculoskeletal morbidity codes used in routine primary care by body region, and to determine the annual consultation prevalence of regional musculoskeletal problems.</p> <p>Methods</p> <p>Musculoskeletal codes within the Read morbidity Code system were identified and grouped by relevant body region by four GPs. Consultations with these codes were then extracted from the recorded consultations at twelve general practices contributing to a general practice consultation database (CiPCA). Annual consultation prevalence per 10,000 registered persons for the year 2006 was determined, stratified by age and gender, for problems in individual regions and for problems affecting multiple regions.</p> <p>Results</p> <p>5,908 musculoskeletal codes were grouped into regions. One in seven of all recorded consultations were for a musculoskeletal problem. The back was the most common individual region recorded (591 people consulting per 10,000 registered persons), followed by the knee (324/10,000). In children, the foot was the most common region. Different age and gender trends were apparent across body regions although women generally had higher consultation rates. The annual consultation-based prevalence for problems encompassing more than one region was 556 people consulting per 10,000 registered persons and increased in older people and in females.</p> <p>Conclusions</p> <p>There is an extensive and varied regional musculoskeletal workload in primary care. Musculoskeletal problems are a major constituent of general practice. The output from this study can be used as a resource for planning future studies.</p

Risk factors for delayed presentation and referral of symptomatic cancer: Evidence for common cancers

Background:It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation.Methods:We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these.Results:Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, ‘misdiagnosis’ occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results.Conclusion:Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately. © 2009 Cancer Research UK All rights reserved

Intravenous co-amoxiclav to prevent infection after operative vaginal delivery: the ANODE RCT.

BACKGROUND: Sepsis is a leading cause of direct and indirect maternal death in both the UK and globally. All forms of operative delivery are associated with an increased risk of sepsis, and the National Institute for Health and Care Excellence's guidance recommends the use of prophylactic antibiotics at all caesarean deliveries, based on substantial randomised controlled trial evidence of clinical effectiveness. A Cochrane review, updated in 2017 (Liabsuetrakul T, Choobun T, Peeyananjarassri K, Islam QM. Antibiotic prophylaxis for operative vaginal delivery. Cochrane Database Syst Rev 2017;8:CD004455), identified only one small previous trial of prophylactic antibiotics following operative vaginal birth (forceps or ventouse/vacuum extraction) and, given the small study size and extreme result, suggested that further robust evidence is needed. OBJECTIVES: To investigate whether or not a single dose of prophylactic antibiotic following operative vaginal birth is clinically effective for preventing confirmed or presumed maternal infection, and to investigate the associated impact on health-care costs. DESIGN: A multicentre, randomised, blinded, placebo-controlled trial. SETTING: Twenty-seven maternity units in the UK. PARTICIPANTS: Women who had an operative vaginal birth at ≥ 36 weeks' gestation, who were not known to be allergic to penicillin or constituents of co-amoxiclav and who had no indication for ongoing antibiotics. INTERVENTIONS: A single dose of intravenous co-amoxiclav (1 g of amoxicillin/200 mg of clavulanic acid) or placebo (sterile saline) allocated through sealed, sequentially numbered, indistinguishable packs. MAIN OUTCOME MEASURES: Primary outcome - confirmed or suspected infection within 6 weeks of giving birth. Secondary outcomes - severe sepsis, perineal wound infection, perineal pain, use of pain relief, hospital bed stay, hospital/general practitioner visits, need for additional perineal care, dyspareunia, ability to sit comfortably to feed the baby, maternal general health, breastfeeding, wound breakdown, occurrence of anaphylaxis and health-care costs. RESULTS: Between March 2016 and June 2018, 3427 women were randomised: 1719 to the antibiotic arm and 1708 to the placebo arm. Seven women withdrew, leaving 1715 women in the antibiotic arm and 1705 in the placebo arm for analysis. Primary outcome data were available for 3225 out of 3420 women (94.3%). Women randomised to the antibiotic arm were significantly less likely to have confirmed or suspected infection within 6 weeks of giving birth (180/1619, 11%) than women randomised to the placebo arm (306/1606, 19%) (relative risk 0.58, 95% confidence interval 0.49 to 0.69). Three serious adverse events were reported: one in the placebo arm and two in the antibiotic arm (one was thought to be causally related to the intervention). LIMITATIONS: The follow-up rate achieved for most secondary outcomes was 76%. CONCLUSIONS: This trial has shown clear evidence of benefit of a single intravenous dose of prophylactic co-amoxiclav after operative vaginal birth. These results may lead to reconsideration of official policy/guidance. Further analysis of the mechanism of action of this single dose of antibiotic is needed to investigate whether earlier, pre-delivery or repeated administration could be more effective. Until these analyses are completed, there is no indication for administration of more than a single dose of prophylactic antibiotic, or for pre-delivery administration. TRIAL REGISTRATION: Current Controlled Trials ISRCTN11166984. 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. 23, No. 54. See the National Institute for Health Research Journals Library website for further project information

Distributed situation awareness in dynamic systems: Theoretical development and application of an ergonomics methodology

The purpose of this paper is to propose foundations for a theory of situation awareness based on the analysis of interactions between agents (i.e., both human and non-human) in subsystems. This approach may help promote a better understanding of technology-mediated interaction in systems, as well as helping in the formulation of hypotheses and predictions concerning distributed situation awareness. It is proposed that agents within a system each hold their own situation awareness which may be very different from (although compatible with) other agents. It is argued that we should not always hope for, or indeed want, sharing of this awareness, as different system agents have different purposes. This view marks situation awareness as a 1 dynamic and collaborative process that binds agents together on tasks on a moment-by-moment basis. Implications of this viewpoint for development of a new theory of, and accompanying methodology for, distributed situation awareness are offered

Enteral lactoferrin supplementation for very preterm infants: a randomised placebo-controlled trial

Background Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow's milk, prevents infections and associated complications. The aim of this large randomised controlled trial was to collect data to enhance the validity and applicability of the evidence from previous trials to inform practice. Methods In this randomised placebo-controlled trial, we recruited very preterm infants born before 32 weeks' gestation in 37 UK hospitals and younger than 72 h at randomisation. Exclusion criteria were presence of a severe congenital anomaly, anticipated enteral fasting for longer than 14 days, or no realistic prospect of survival. Eligible infants were randomly assigned (1:1) to receive either enteral bovine lactoferrin (150 mg/kg per day; maximum 300 mg/day; lactoferrin group) or sucrose (same dose; control group) once daily until 34 weeks' postmenstrual age. Web-based randomisation minimised for recruitment site, gestation (completed weeks), sex, and single versus multifetal pregnancy. Parents, caregivers, and outcome assessors were unaware of group assignment. The primary outcome was microbiologically confirmed or clinically suspected late-onset infection (occurring >72 h after birth), which was assessed in all participants for whom primary outcome data was available by calculating the relative risk ratio with 95% CI between the two groups. The trial is registered with the International Standard Randomised Controlled Trial Number 88261002. Findings We recruited 2203 participants between May 7, 2014, and Sept 28, 2017, of whom 1099 were assigned to the lactoferrin group and 1104 to the control group. Four infants had consent withdrawn or unconfirmed, leaving 1098 infants in the lactoferrin group and 1101 in the sucrose group. Primary outcome data for 2182 infants (1093 [99·5%] of 1098 in the lactoferrin group and 1089 [99·0] of 1101 in the control group) were available for inclusion in the modified intention-to-treat analyses. 316 (29%) of 1093 infants in the intervention group acquired a late-onset infection versus 334 (31%) of 1089 in the control group. The risk ratio adjusted for minimisation factors was 0·95 (95% CI 0·86–1·04; p=0·233). During the trial there were 16 serious adverse events for infants in the lactoferrin group and 10 for infants in the control group. Two events in the lactoferrin group (one case of blood in stool and one death after intestinal perforation) were assessed as being possibly related to the trial intervention. Interpretation Enteral supplementation with bovine lactoferrin does not reduce the risk of late-onset infection in very preterm infants. These data do not support its routine use to prevent late-onset infection and associated morbidity or mortality in very preterm infants. Funding UK National Institute for Health Research Health Technology Assessment programme (10/57/49)