Maternal and perinatal outcomes in women planning vaginal birth after caesarean (VBAC) at home in England: secondary analysis of the Birthplace national prospective cohort study

OBJECTIVE: To compare vaginal birth rates in women planning vaginal birth after caesarean (VBAC) at home versus in an obstetric unit (OU) and explore transfer rates in women planning home VBAC. DESIGN: Prospective cohort study. SETTING: OUs and planned home births in England. POPULATION: 1436 women planning VBAC in the Birthplace cohort, including 209 planning home VBAC. METHODS: We used Poisson regression to calculate relative risks adjusted for maternal characteristics. MAIN OUTCOME MEASURES: MAIN OUTCOMES: (i) vaginal birth and (ii) transfer from planned home birth to OU during labour or immediately after birth. SECONDARY OUTCOMES: (i) composite of maternal blood transfusion or admission to higher level care, (ii) stillbirth or Apgar score <7 at 5 minutes, (iii) neonatal unit admission. RESULTS: Planned VBAC at home was associated with a statistically significant increase in the chances of having a vaginal birth compared with planned VBAC in an OU (adjusted relative risk 1.15, 95% confidence interval 1.06-1.24). The risk of an adverse maternal outcome was around 2-3% in both settings, with a similar risk of an adverse neonatal outcome. Transfer rates were high (37%) and varied markedly by parity (para 1, 56.7% versus para 2+, 24.6%). CONCLUSION: Women in the cohort who planned VBAC at home had an increased chance of a vaginal birth compared with those planning VBAC in an OU, but transfer rates were high, particularly for women with only one previous birth, and the risk of an adverse maternal or perinatal outcome was around 2-3%. No change in guidance can be recommended. TWEETABLE ABSTRACT: Higher vaginal birth rates in planned VBAC at home versus in OU but 2-3% adverse outcomes and high transfer rate

Underlying barriers to referral to paediatric palliative care services: knowledge and attitudes of healthcare professionals in a paediatric tertiary care centre in the United Kingdom

Referrals to children’s palliative care services typically occur late in the illness trajectory, with many children who would benefit not referred at all. Previous studies report health care professionals’ (HCPs) assessment of various parent-related factors as barriers to referral. We conducted a cross-sectional survey of HCPs working in a paediatric tertiary care hospital in the United Kingdom, with an established paediatric palliative care team, to explore staff perceptions of barriers, knowledge and attitudes, with the aim of developing interventions to increase patient access to palliative care services. Survey respondents evidenced good knowledge of the principles of palliative care in closed questions, but their attitudes expressed in open-text questions and reported reasons to refer to a palliative care service demonstrated an association of palliative care with death and dying. We suggest that the association of palliative care with end of life may be a modifiable factor relevant to late and non-referral and deserving of further investigation and attention in education and training

Risk of myocardial infarction and stroke after acute infection or vaccination.

BACKGROUND: There is evidence that chronic inflammation may promote atherosclerotic disease. We tested the hypothesis that acute infection and vaccination increase the short-term risk of vascular events. METHODS: We undertook within-person comparisons, using the case-series method, to study the risks of myocardial infarction and stroke after common vaccinations and naturally occurring infections. The study was based on the United Kingdom General Practice Research Database, which contains computerized medical records of more than 5 million patients. RESULTS: A total of 20,486 persons with a first myocardial infarction and 19,063 persons with a first stroke who received influenza vaccine were included in the analysis. There was no increase in the risk of myocardial infarction or stroke in the period after influenza, tetanus, or pneumococcal vaccination. However, the risks of both events were substantially higher after a diagnosis of systemic respiratory tract infection and were highest during the first three days (incidence ratio for myocardial infarction, 4.95; 95 percent confidence interval, 4.43 to 5.53; incidence ratio for stroke, 3.19; 95 percent confidence interval, 2.81 to 3.62). The risks then gradually fell during the following weeks. The risks were raised significantly but to a lesser degree after a diagnosis of urinary tract infection. The findings for recurrent myocardial infarctions and stroke were similar to those for first events. CONCLUSIONS: Our findings provide support for the concept that acute infections are associated with a transient increase in the risk of vascular events. By contrast, influenza, tetanus, and pneumococcal vaccinations do not produce a detectable increase in the risk of vascular events

Course-based Science Research Promotes Learning in Diverse Students at Diverse Institutions

Course-based research experiences (CREs) are powerful strategies for spreading learning and improving persistence for all students, both science majors and nonscience majors. Here we address the crucial components of CREs (context, discovery, ownership, iteration, communication, presentation) found across a broad range of such courses at a variety of academic institutions. We also address how the design of a CRE should vary according to the background of student participants; no single CRE format is perfect. We provide a framework for implementing CREs across multiple institutional types and several disciplines throughout the typical four years of undergraduate work, designed to a variety of student backgrounds. Our experiences implementing CREs also provide guidance on overcoming barriers to their implementation

Understanding the stabilizing effect of histidine on mAb aggregation: a molecular dynamics study.

Histidine, a widely used buffer in monoclonal antibody (mAb) formulations, is known to reduce antibody aggregation. While experimental studies suggest a nonelectrostatic, nonstructural (relating to secondary structure preservation) origin of the phenomenon, the underlying microscopic mechanism behind the histidine action is still unknown. Understanding this mechanism will help evaluate and predict the stabilizing effect of this buffer under different experimental conditions and for different mAbs. We have used all-atom molecular dynamics simulations and contact-based free energy calculations to investigate molecular-level interactions between the histidine buffer and mAbs, which lead to the observed stability of therapeutic formulations in the presence of histidine. We reformulate the Spatial Aggregation Propensity index by including the buffer-protein interactions. The buffer adsorption on the protein surface leads to lower exposure of the hydrophobic regions to water. Our analysis indicates that the mechanism behind the stabilizing action of histidine is connected to the shielding of the solvent-exposed hydrophobic regions on the protein surface by the buffer molecules

Implications of the problem orientated medical record (POMR) for research using electronic GP databases: a comparison of the Doctors Independent Network Database (DIN) and the General Practice Research Database (GPRD).

Background The General Practice Research Database (GPRD) and Doctor's Independent Network Database (DIN), are large electronic primary care databases compiled in the UK during the 1990s. They provide a valuable resource for epidemiological and health services research. GPRD (based on VAMP) presents notes as a series of discrete episodes, whereas DIN is based on a system (MEDITEL) that used a Problem Orientated Medical Record (POMR) which links prescriptions to diagnostic problems. We have examined the implications for research of these different underlying philosophies. Methods Records of 40,183 children from 141 practices in DIN and 76,310 from 464 practices in GRPD who were followed to age 5 were used to compare the volume of recording of prescribing and diagnostic codes in the two databases. To assess the importance and additional value of the POMR within DIN, the appropriateness of diagnostic linking to skin emollient prescriptions was investigated. Results Variation between practices for both the number of days on which prescriptions were issued and diagnoses were recorded was marked in both databases. Mean number of "prescription days" during the first 5 years of life was similar in DIN (19.5) and in GPRD (19.8), but the average number of "diagnostic days" was lower in DIN (15.8) than in GPRD (22.9). Adjustment for linkage increased the average "diagnostic days" to 23.1 in DIN. 32.7% of emollient prescriptions in GPRD appeared with an eczema diagnosis on the same day compared to only 19.4% in DIN; however, 86.4% of prescriptions in DIN were linked to an earlier eczema diagnosis. More specifically 83% of emollient prescriptions appeared under a problem heading of eczema in the 121 practices that were using problem headings satisfactorily. Conclusion Prescribing records in DIN and GPRD are very similar, but the usage of diagnostic codes is more parsimonious in DIN because of its POMR structure. Period prevalence rates will be underestimated in DIN unless this structure is taken into account. The advantage of the POMR is that in 121 of 141 practices using problem headings as intended, most prescriptions can be linked to a problem heading providing a specific reason for their issue

Effect of Nuclear Quadrupole Interaction on the Relaxation in Amorphous Solids

Recently it has been experimentally demonstrated that certain glasses display an unexpected magnetic field dependence of the dielectric constant. In particular, the echo technique experiments have shown that the echo amplitude depends on the magnetic field. The analysis of these experiments results in the conclusion that the effect seems to be related to the nuclear degrees of freedom of tunneling systems. The interactions of a nuclear quadrupole electrical moment with the crystal field and of a nuclear magnetic moment with magnetic field transform the two-level tunneling systems inherent in amorphous dielectrics into many-level tunneling systems. The fact that these features show up at temperatures $T<100mK$, where the properties of amorphous materials are governed by the long-range $R^{-3}$ interaction between tunneling systems, suggests that this interaction is responsible for the magnetic field dependent relaxation. We have developed a theory of many-body relaxation in an ensemble of interacting many-level tunneling systems and show that the relaxation rate is controlled by the magnetic field. The results obtained correlate with the available experimental data. Our approach strongly supports the idea that the nuclear quadrupole interaction is just the key for understanding the unusual behavior of glasses in a magnetic field.Comment: 18 pages, 9 figure

The Birthplace in England national prospective cohort study: further analyses to enhance policy and service delivery decision-making for planned place of birth

Background: Evidence from the Birthplace in England Research Programme supported a policy of offering ‘low risk’ women a choice of birth setting, but a number of unanswered questions remained. Aims: This project aimed to provide further evidence to support the development and delivery of maternity services and inform women’s choice of birth setting: specifically, to explore maternal and organisational factors associated with intervention, transfer and other outcomes in each birth setting in ‘low risk’ and ‘higher risk’ women. Design: Five component studies using secondary analysis of the Birthplace prospective cohort study (studies 2–5) and ecological analysis of unit/NHS trust-level data (studies 1 and 5). Setting: Obstetric units (OUs), alongside midwifery units (AMUs), freestanding midwifery units (FMUs) and planned home births in England. Participants: Studies 1–4 focused on ‘low risk’ women with ‘term’ pregnancies planning vaginal birth in 43 AMUs (n = 16,573), in 53 FMUs (n = 11,210), at home in 147 NHS trusts (n = 16,632) and in a stratified, random sample of 36 OUs (n = 19,379) in 2008–10. Study 5 focused on women with pre-existing medical and obstetric risk factors (‘higher risk’ women). Main outcome measures: Interventions (instrumental delivery, intrapartum caesarean section), a measure of low intervention (‘normal birth’), a measure of spontaneous vaginal birth without complications (‘straightforward birth’), transfer during labour and a composite measure of adverse perinatal outcome (‘intrapartum-related mortality and morbidity’ or neonatal admission within 48 hours for > 48 hours). In studies 1 and 3, rates of intervention/maternal outcome and transfer were adjusted for maternal characteristics. Analysis: We used (a) funnel plots to explore variation in rates of intervention/maternal outcome and transfer between units/trusts, (b) simple, weighted linear regression to evaluate associations between unit/trust characteristics and rates of intervention/maternal outcome and transfer, (c) multivariable Poisson regression to evaluate associations between planned place of birth, maternal characteristics and study outcomes, and (d) logistic regression to investigate associations between time of day/day of the week and study outcomes. Results: Study 1 – unit-/trust-level variations in rates of interventions, transfer and maternal outcomes were not explained by differences in maternal characteristics. The magnitude of identified associations between unit/trust characteristics and intervention, transfer and outcome rates was generally small, but some aspects of configuration were associated with rates of transfer and intervention. Study 2 – ‘low risk’ women planning non-OU birth had a reduced risk of intervention irrespective of ethnicity or area deprivation score. In nulliparous women planning non-OU birth the risk of intervention increased with increasing age, but women of all ages planning non-OU birth experienced a reduced risk of intervention. Study 3 – parity, maternal age, gestational age and ‘complicating conditions’ identified at the start of care in labour were independently associated with variation in the risk of transfer in ‘low risk’ women planning non-OU birth. Transfers did not vary by time of day/day of the week in any meaningful way. The duration of transfer from planned FMU and home births was around 50–60 minutes; transfers for ‘potentially urgent’ reasons were quicker than transfers for ‘non-urgent’ reasons. Study 4 – the occurrence of some interventions varied by time of the day/day of the week in ‘low risk’ women planning OU birth. Study 5 – ‘higher risk’ women planning birth in a non-OU setting had fewer risk factors than ‘higher risk’ women planning OU birth and these risk factors were different. Compared with ‘low risk’ women planning home birth, ‘higher risk’ women planning home birth had a significantly increased risk of our composite adverse perinatal outcome measure. However, in ‘higher risk’ women, the risk of this outcome was lower in planned home births than in planned OU births, even after adjustment for clinical risk factors. Conclusions: Expansion in the capacity of non-OU intrapartum care could reduce intervention rates in ‘low risk’ women, and the benefits of midwifery-led intrapartum care apply to all ‘low risk’ women irrespective of age, ethnicity or area deprivation score. Intervention rates differ considerably between units, however, for reasons that are not understood. The impact of major changes in the configuration of maternity care on outcomes should be monitored and evaluated. The impact of non-clinical factors, including labour ward practices, staffing and skill mix and women’s preferences and expectations, on intervention requires further investigation. All women planning non-OU birth should be informed of their chances of transfer and, in particular, older nulliparous women and those more than 1 week past their due date should be advised of their increased chances of transfer. No change in the guidance on planning place of birth for ‘higher risk’ women is recommended, but research is required to evaluate the safety of planned AMU birth for women with selected relatively common risk factors. Funding: The National Institute for Health Research Health Services and Delivery Research programme